COLUMBIA  LIBRARIES  OFFSITE 

HEALTH  SCIENCES  STANDARD 


HX00034053 


■^e^\^ 


o 


Olfllumbia  Hmupraitg 
in  ti^e  Olitg  of  N^m  ^ork 


.^v:.s...C...^.-.U^Y.l.hex 


Printed  by 

H.  K.  Lewis,  136  Gower  Street 

London. 


Digitized  by  the  Internet  Archive 

in  2010  with  funding  from 

Open  Knowledge  Commons 


http://www.archive.org/details/onbilejaundicebiOOIegg 


H  ^    L.«vrui  J\»blirt»«r,  13b  !.* 


ON    THE    BILE 


JAUNDICE 


BILIOUS     DISEASES 


J.  WICKHAM  LEGG 


FELLOW  OF  THE  ROYAL   COLLEGE  OF  PHYSICIANS    OF    LONDON 

ASSISTANT   PHYSICIAN    TO     SAINT    BARTHOLOMEW'S   HOSPITAL   AND     LECTURER    ON      PATHOLOGICAL 

ANATOMY  IN   THE  MEDICAL   SCHOOL 


La  bile  est  un  liquide  dont  VHude  iniiresse  au  plus  haul 
point  le  physiologiste  et  le  midecin.  Les  difficultis  dont  est 
entouri  son  histoire  physiologique  font  qu'elle  est  encore  fort 
obscure. 

Claude  Bernard. 


NEW  YORK 
D.  APPLETON  &  Co.,  I,  3  &  5  BOND  STREET. 

M.DCCCLXXX. 


i  < 


To 

HIS  ROYAL  HIGHNESS 

THE   PRINCE  LEOPOLD 


The  following  pages  are,  with  all  respect,  inscribed,  in 
grateful  acknowledgement  of  many  favours, 

by  HIS  ROYAL  HIGHNESS' 
most  dutiful, 

most  devoted, 

and  most  humble  servant, 

J.   WICKHAM   LEGG. 


PREFACE 

The  liver  Is  the  largest  gland  in  the  body ;  and  its 
importance  to  the  animal  oeconomy  is  shown  by  its 
presence  in  the  lowest  tribes,  and  by  its  early  ap- 
pearance in  the  developement  of  the  embryo.  It  might 
be  looked  for  that  an  organ  so  large  and  so  constantly 
seen  should  be  endowed  with  manifold  functions  ;  but 
for  the  demonstration  of  these  we  have  had  to  wait 
almost  to  our  own  time,  for  it  is  hardly  more  than 
thirty  years  ago  since  Claude  Bernard  began  a  series 
of  discoveries,  which  have  ended  in  the  restoration  to 
the  liver  of  all  the  functions  which  it  formerly  possessed, 
acccording  to  the  speculations  which  we  find  recorded 
in  the  writings  of  Galen.  That  these  functions  become 
disturbed  in  disease  is  a  proposition  of  great  likelihood  ; 
and  the  liver  may  hereafter  prove  one  of  the  most  im- 
portant of  the  organs  concerned  in  all  matters  of 
nutrition,  growth,  sanguification,  and  animal  life.  But 
as  so  short  a  time  has  gone  by  since  these  functions 
became  known  in   health,  very  little,   if  any,  progress 


viii  Preface. 

has  been  made  in  the  knowledge  of  the  changes  which 
they  undergo  in  disease.  Some  observations  made  at 
St.  Bartholomew's  Hospital  in  the  year  1873,  on  the 
amount  of  glycogen  in  the  liver  in  jaundice,  are  among 
the  first  attempts  to  tread  this  path  of  experiment. 

The  following  pages  are  devoted  to  that  office  of  the 
liver  which,  for  two  hundred  years,  was  the  only  one 
allowed  by  physiologists  ;  that  is,  the  secretion  of  bile. 
The  early  chapters  treat  of  the  chemistry  and  physio- 
logy of  this  humour.  The  first  of  these  may  be 
thought  to  be  in  a  tolerably  satisfactory  state,  since  so 
much  light  was  thrown  upon  the  chemistry  of  the  bile 
acids  by  the  labours  of  Adolf  Strecker  thirty  years  ago. 
The  physiology  of  the  bile  is  still  surrounded  by  a 
darkness  almost  Egyptian  ;  and  it  may  surprise  many 
to  find  how  little  knowledge  there  is  of  a  humour 
which  has  been  carefully  studied  for  over  two  thousand 
years,  and  which  already  filled  a  great  place  in  the 
physiology  of  the  Timceiis.  Much  of  this  obscurity  is 
doubtless  due  to  the  place  which  physiology  holds 
among  the  sciences  ;  little  progress  can  be  made  till 
the  others  beneath  have  well  nigh  reached  perfection ; 
and  still   more  to  the  point  at  which  the  bile  is  dis- 


Preface.  ix 

charged,  into  the  tipper  part  of  the  intestine,  where  it 
cannot  conveniently  be  collected  and  measured,  as  may 
readily  be  done  with  other  secretions,  such  as  the 
urine.  A  bar,  not  to  be  overcome,  seems  to  be  thus 
placed  by  nature  herself  in  the  way  of  much  increase 
of  knowledge. 

In  several  chapters,  the  phaenomena  caused  by  an 
obstruction  to  the  discharge  of  the  bile  into  the  intestine 
have  been  dealt  with  ;  and  in  those  which  follow,  an  ac- 
count has  been  given  of  certain  species  of  jaundice, 
where  an  obstruction  to  the  flow  of  bile  cannot  at  once 
and  without  trouble  be  discovered  after  death.  And  to 
those  species  of  jaundice,  the  cause  of  which  is  obscure, 
I  have  confined  myself;  though,  nevertheless,  I  have 
not  fallen  into  the  un-English  virtue  of  consistency  ;  for, 
as  part  of  the  chapter  on  icterus  infantum^  I  have  dealt 
with  the  appearances  which  follow  congenital  constriction 
of  the  gall  ducts,  which  may  by  some  be  considered  only 
a  variety  of  the  foregoing  icterus.  In  a  work,  too,  which 
deals  with  disorders  of  the  bile,  some  account  of  gall- 
stones might  be  looked  for ;  but  the  space  required  for 
anything  like  a  full  discussion  of  the  phaenomena  caused 
by  these   bodies   would   be    very    great,  and    I    have 


X  Preface. 

already  gone  beyond  the  bounds  which  were  set  when 
the  printing  of  this  book  was  begun.  Sometimes,  too, 
I  have  had  to  travel  twice  over  the  same  ground  in 
dealing  with  the  physiology  of  the  bile  and  the  doc- 
trine of  jaundice  ;  and  there  thus  arises  the  appear- 
ance of  repetition,  very  needful,  however,  to  the  right 
understanding  of  the  matter  in  hand. 

In  the  last  chapter  I  have  specially  considered  the 
meaning  of  "  bilious  diseases  "  ;  and  I  have  proposed 
that  the  word  "bilious"  should  no  longer  be  used  as 
an  adjective  to  diseases.  I  am  led  to  this  proposal  by 
the  great  confusion  which  exists  as  to  the  definition  of 
the  word  ;  nearly  every  country,  and  I  might  say,  nearly 
every  author,  having  a  different  sense  for  it.  In  this 
work,  "bilious,"  when  used  with  the  word  headache, 
attack,  or  the  like,  always  connotes  a  gastric  catarrh. 

I  am  glad  of  this  opportunity  to  thank  Professor 
Chauveau  and  the  French  Government  for  the  hospi- 
tality shown  to  a  foreigner  in  providing  the  means  for 
some  experiments  which  were  made  at  Lyons  nearly  two 
years  ago,  and  of  which  I  have  spoken  in  the  fourteenth 
Chapter  of  this  work.  All  the  appliances  of  one  of  the  best 
furnished  laboratories  in  Europe  were  set  before  me  ;   a 


Preface.  xi 

staff  of  able  assistants  was  told  off  to  give  me  whatever  aid 
was  needful ;  and  the  cost  of  the  whole  series  of  experi- 
ments was  borne  by  the  French  Government.  It  would 
be  indeed  ungrateful  not  to  acknowledge,  even  in  this 
feeble  way,  the  welcome  which  I  received.  It  may  strike 
others,  besides  myself,  that  much  light  would  have  been 
thrown  upon  many  other  points  in  this  work  by  well- 
devised  experiments.  But  in  England,  for  some  years 
past,  all  experiments  on  animals  have  been  practically 
forbidden.  We  pay  for  our  freedom  in  some  matters 
by  being  at  the  mercy  of  every  truculent  agitation  in 
others ;  and  a  senseless  outcry,  by  putting  on  the 
sacred  garb  of  religion  and  morality,  from  the  highest 
authorities  in  which  it  receives  no  countenance,  but 
rather  condemnation,  has  prospered  in  its  designs  for  a 
time.  In  the  plan  of  the  book  I  have  therefore  followed 
the  method  of  Albert  the  Great,  rather  than  the  higher 
path  shown  us  by  Francis  Bacon,  and  our  own  great 
predecessor  at  St.  Bartholomew's,  William  Harvey.  For 
whatever  imperfections  there  may  be  in  the  method  fol- 
lowed, the  reader  must  blame  those  Manichaean  teach- 
ings, which,  harmful  as  they  are,  are  almost  as  old  as  the 
human  race  itself,  and  the  germs  of  which  seem  to  exist 


xii  Preface. 

everywhere,  ready  to  burst  into  a  fresh  life,  even  amongst 
those  who  claim  to  be  most  orthodox  and  sincere  in 
their  morals  and  belief. 

London,  Dec.  20,  1879. 


TABLE    OF    CONTENTS. 


CHAPTER   I. 

PAGE 

Chemistry  of  the  Bile  ;  the  Bile  Acids i 


CHAPTER  11. 
The  Bile  Pigments '  .        .        26 

CHAPTER  HI. 

The  Fats,  Salts,  Gases,  and  other  Constituents  of  the  Bile       .        50 

CHAPTER  IV 

Physical  and  Chemical  Appearances  of  Human  Bile  ...        58 

CHAPTER  V. 

History  of  the  Physiology  of  the  Bile  ;    the  Sources  of  the  Bile 

in  the  ceconomy 73 

CHAPTER  VI. 

The  Amount  of  Bile  Secreted  in  Health,  and  the  Agents  which 

affect  it 94 

CHAPTER  VII. 
The  Office  of  the  Bile 132 

CHAPTER  VIII. 

The  Action  of  Drugs  upon  the  Secretion  of  the  Bile    ...        .      157 


xiv  Table  of  Contents. 

CHAPTER   IX. 

PAGE 

The  Physiological  Action  of  the  Bile 187 

CHAPTER  X. 
The  Etymology,  History,  and  Etiology  of  Jaundice         .        .        .      225 

CHAPTER  XI. 
The  Symptoms  of  Jaundice 257 

CHAPTER  XII. 
The  Complications  of  Jaundice 298 

CHAPTER  XIII. 
The  Morbid  Anatomy  of  Jaundice 341 

CHAPTER  XIV. 
The  Functions  of  the  Liver  in  Jaundice 363 

CHAPTER  XV. 
The  Diagnosis  and  Prognosis  of  Jaundice 374 

CHAPTER  XVI. 
The  Treatment  of  Jaundice 380 

CHAPTER  XVII. 
Icterus  Simplex 388 

CHAPTER  XVIII. 
Icterus  Epidemius 406 


Table  of  Contents.  xv 

CHAPTER  XIX. 

PAGE 

Icterus   Gravis,  and  the  History  and  Etiology  of  Acute  Yellow 

Atrophy       ............       412 

CHAPTER  XX. 

The  Symptoms  of  Acute  Yellow  Atrophy,  its  Prodroma,  the 
Jaundice,  Nervous  Symptoms,  Hemorrhagic  Diathesis,  and 
THE  Rise  in  temperature  and  pulse  seen  in  Acute  Yellow 
Atrophy,  decrease  in  liver  and  increase  in  spleen,  the 
state  of  the  urine  and  the  blood 437 

CHAPTER  XXI. 

The  Morbid  Anatomy  and  Pathology  of  Acute  Yellow  Atrophy    .      486 

CHAPTER  XXII. 

The     Diagnosis,     Prognosis,    and    Treatment    of    Acute    Yellow 

Atrophy 538 

CHAPTER  XXIII. 
Yellow  Fever:    "Bilious  Typhoid" 546 

CHAPTER   XXIV. 


Phosphorus  Poisoning 


557 


CHAPTER   XXV. 
Jaundice  after  Poisoning  by  Arsenic,  Antimony,  and  other  Bodies      578 

CHAPTER   XXVI. 
Icterus  Febrilis 584 

CHAPTER   XXVII. 
Icterus  Syphiliticus,  Icterus  a  venenis,  snake  bites         .        .        .      609 


xvi  Table  of  Contents. 

CHAPTER  XXVIII. 


PAGE 


Icterus  Gravidarum,  Icterus  Embryonum,  Icterus  Neonatorum, 
Icterus  Infantum,  with  Congenital  Defect  of  the  Gall 
Ducts,  Icterus  Menstrualis 615 

CHAPTER   XXIX. 
On  Bilious  Diseases 651 

CHAPTER  XXX. 

Bibliography    of    Icterus   Epidemius,  Acute  Yellow  Atrophy,  and 

Congenital  Defect  of  the  Gall  Ducts 665 


ERRATA. 

p.  72,  Heinrich  Bayer's  paper  on  human  cholalic  acid  appears  in  the  September 
number  of  Hoppe-Seyler's  Zeitschriftf.  phys.  Chemie,  1879. 
p.  148,  second  Hne  from  top,  for  chloidic  read  choloidic. 
p.  485,  third  line  from  top,  for  blood  from  the  urine  read  blood  from  the  arm. 
p.  491,  third  line  from  top,  for  Moraud  read  Morand. 


CHAPTER  I. 

Chemistry  of  the  Bile. 

The  bile  of  vertebrates  is  made  up  chiefly  of  three 
groups  of  bodies  :  the  bile  acids  in  combination 
with  soda ;  the  bile  pigments  ;  and  fats,  especially 
cholestearin.  Of  these,  the  bile  acids  are  by  far  the 
most  noteworthy,  as  they  are  found  in  greatest  amount, 
and  are  the  most  important  in  their  physiological  action 
and  relations. 

It  cannot  be  looked  for  that  much  information  should 
have  been  gained  as  to  the  chemical  composition  of 
the  bile  before  the  time  of  Lavoisier.  But  it  needed 
no  chemist  to  say  that  the  bile  held  a  pigment :  and 
it  was  well  known  that  it  possessed  the  power  of 
cleaning  stuffs  like  a  soap,*  Robert  Ramsay  appears 
to  have  been  the  first  to  note  the  resin  in  the 
bile  which  was  afterwards  to  be  known  as  the  bile 
acids, t  but  it  is  to  the  very  beginning  of  this  century 
that  we  must  look  for  the  first  satisfactory  attempts  at 
an  analysis  of  the  bile. 

Thenard,  by  throwing  down  the  bile  with  the  acetate  of 

*  Cadet,  Memoires  de  V Academic  royale  dcs  Sciences,  annee  1767,  Paris  1770, 
p.  483.  "  Je  puis  done  enfin  conclure  que  la  bile  est  un  veritable  savon  compose 
d'une  graisse  animale  et  de  la  base  alkaline  du  sel  marin,  et  du  sel  marin  lui- 
meme,  d'un  sel  essentiel  de  la  nature  du  sucre  de  lait  et  d'une  terre  calcaire  qui 
participe  un  peu  du  fer."  For  history  of  earlier  opinions,  see  Haller,  Elem.  phys. 
Lugd.  Bat.  1764,  t.  vi.  p.  542.  Lib.  xxiii.  §  iii.  For  history  up  to  his  own  time, 
see  Platner,  Uebey  die  Natur  u.  den  Niitzen  der  Galle,  Heidelberg,  1845. 

f  Roberti  Ramsay,  Diss.  Med.  inaug.  de  bile,  Edinb.  1757,  in  Sandifort's  The- 
saurus Dissertationum,  Roterodami,  1769,  vol.  ii.  p.  567.  "  Bilis  materiis  constare 
videtur  tribus  diversis,  parte  scilicet  aquosa ;  parte  resinosa,  spiritu  vini,  non  aqua 
solubili ;  parte  denique  viscida  putrescente,  neque  aqua,  neque  spiritu  vini  solu- 
bili". 

B 


2  Chemistry  of  the  Bile. 

lead,  an  agent  which  has  proved  so  useful  in  the  manipu- 
lation of  this  humour,  obtained  a  body  which  he  named 
picromel,*  from  its  taste.  This  appears  to  have  been  a 
collection  of  the  impure  bile  acids.  He  also  separated 
a  resin  or  fat,  to  which  he  attributed  in  chief  the  colour 
and  taste  of  the  bile.  He  opposed  the  ancient  belief 
that  the  bile  was  a  kind  of  soap.  He  noted  the 
amount  of  soda  salts,  the  presence  of  traces  of  iron, 
and  that  the  solids  were  about  ^  to  ^.f 

Berzelius  followed  hard  upon  Thenard  with  his  in- 
vestigations on  the  bile.  He  thought  it  probable  that 
the  picromel  and  resin  of  Thenard  were  but  one  body. 
Berzelius  named  this  biliary  material  ;J  it  was,  in  his 
opinion,  free  from  nitrogen  but  akin  to  albumen. 

Tiedemann  and  Gmelin  report  a  large  number  of 
analyses  of  the  bile  in  their  work  on  the  digestion  of 
animals. §  They  claim  to  have  noted  the  presence 
of  cholestearin  in  the  bile  in  the  year  1823,  before  they 
were  acquainted  with  the  work  of  Chevreul,  and  also 
to  have  discovered  in  the  winter  of  1823-24  the  action 
of  nitric  acid  on  the  colouring  matter  of  the  bile.||  They 
also  affirmed  the  presence  in  the  bile  of  margarates, 
oleates,  acetates,  cholates,  bicarbonates,  phosphates, 
and  sulphates  of  soda,  and  a  body  which  they  called 
asparagin  but  which  it  is  possible  was  taurin.  A  few 
years  later,  Fromherz  and  Gugert^  came  to  results  very 
nearly  allied  to  those  of  Tiedemann  and  Gmelin.  Ten 
years    later    Demar9ay  succeeded   in   separating  three 

*  Apparently  compounded  of  -riK^os,  bitter,  and  fjuiXi,  honey. 

f  Thenard,  Mcmoircs  de  Physique  et  de  Chimie  de  la  Soc'utc  d^Arcncil,  1807, 
t.  j.  p.  23.     Lu  a  rinstitut  le  2.  floreal,  an  13. 

\  Berzelius,  Schweigger's  yonrnalf.  Chcmic  nnd  Pliysik,  1814,  Bd.  x.  p.  48S. 

§  Tiedemann  and  Gmelin,  Rccherches  cxp.  phys.  ct  cliimiqiics  stir  la  digestion, 
Jourdan's  trans.  Paris,  1826,  lore  partie,  p.  42. 

II  Preface,  p.  xv.  See  Chevreul,  Journal  de  phys.  cxp.  et  path.  1824,  t.  iv.  p. 
257.     He  certainly  found  cholestearin  in  the  bile. 

H  Tromherz  and  Gugert,  Schweigger's  jfuurnal  f.  Chcin.  11.  Phys.  1S27,  Bd.  1. 
p.  68. 


The  Dile  Acids.  3 

acids,  choleic,   choloidic,  and   cholic,   but  not  in   crys- 
tals.* 

Here  the  history  of  the  chemistry  of  the  bile  may  be 
broken  up  into  three  heads  :  and  the  chemistry  of  the 
bile  acids  of  the  pigments,  and  of  cholestearin  con- 
sidered apart. 

The  Bile  Acids,  or  Bilin. 

Crystallised  Bile. — Platner  first  made  out  that  the  resin 
which  bile  held  was  a  crystallisable  body.f  A  few  years 
after,  Adolph  Strecker  discovered  that  this  crystallised 
bile,  obtained  from  ox-bile,  was  made  up  of  the  soda  salts 
of  two  acids  ;  one,  forming  the  greater  part  of  the  com- 
pound, an  acid  containing  nitrogen,  but  free  from  sul- 
phur, which  Strecker  in  the  German  tongue  called 
Cholsdure ;  this  would  be  in  English,  I  suppose,  cholic 
acid,  but  it  is  to-day  very  generally  called  glycocholic 
acid  from  its  relation  to  glycocoll:{  the  other  held 
sulphur  as  well  as  nitrogen,  and  was  called  by  Strecker 
Choleinsdure,  which  in  English  might  be  spoken  of  as 
choleinic  acid  ;  the  name  now  in  general  use  is  tauro- 
cholic  acid  from  its  relation  to  taurin.§ 

For  the  preparation  of  Platner's  crystallised  bile  I 
have  found  a  modification  of  a  process  recommended 
by  Kiihne  very  serviceable. ||  The  bile  of  six  or  eight 
ox-bladders  is  brought  together  in  a  large  Berlin  dish 
and  rubbed    up   into   a  black  mass  with  an  excess  of 


*  Demargay,  Annates  de  chimie  et  de  physique,  1838,  t.  Ixvii.  p.  177. 

t  Platner,  Arch.  f.  Anat.  Phys.  u.s.w.  1844,  p.  94.  See  also  Liebig's  Annalen 
d.  Cheniie  u.  Pharm.  1844,  Bd.  li.  p.  105.  His  work  is  given  at  large  in  his 
pamphlet  published  at  Heidelberg  in  1845  :  Ucher  die  Natur  und  den  Nutzen  der 
Galle. 

%  The  names  glycocholic  and  taurocholic  acid  appear  in  the  first  volume  of 
C.  G.  Lehmann's  Lehrb.  d.  phys.  Chemie,  second  edition,  published  at  Leipzig 
in  1850. 

§  Adolph  Strecker,  Annalen  d.  Chemie  u.  Pharm.  1848,  Bd.  Ixv.  p.  i.  and  Bd. 
Ixvii.  p.  I. 

II   Kiihne,  Lehrbuch  d.  phys.  Chemie,  Leipzig,  1866,  p.  75. 

B  2 


4  Platner^s  Crystallised  Bile, 

animal  charcoal.  This  black  mass  is  then  put  into  a 
wide-mouthed  bottle,  shaken  up  with  ordinary  spirit, 
and  allowed  to  stand  for  several  da3^s.  The  spirit  is 
then  filtered  off  from  the  black  powder,  and  the  filtrate 
evaporated  to  dryness.  The  dr}^  residue  is  then  dis- 
solved in  absolute  alcohol  and  poured  into  a  great  ex- 
cess of  asther  in  a  large  stoppered  bottle.  If  good 
crystals  be  looked  for,  it  is  well  not  to  be  too  spar- 
ing with  the  aether  and  alcohol.  After  a  few  days 
or  even  longer,  the  milky  fluid  becomes  clear,  and  cry- 
stals are  deposited  at  the  bottom.  I  have  found  this 
process  more  serviceable  for  the  manufacture  of  large 
quantities  of  crystallised  bile  than  either  the  process 
of  Hoppe-Sejder  or  Kiihne.  Kiihne,  for  example,  evap- 
orates the  bile  to  one-fourth  of  its  volume,  then  rubs  up 
with  animal  charcoal,  dries  the  mass  at  ioo°  C.  then  puts 
the  whole,  warm,  into  a  large  bottle,  and  exhausts  with 
absolute  alcohol.  After  some  days,  he  filters,  and  throws 
down  with  aether.  This  is  a  wasteful  method,  as  so 
much  of  the  bile  acids  is  retained  in  the  animal  char- 
coal. On  the  other  hand,  Hoppe-Seyler  does  not  pro- 
ceed to  decolorise  the  bile  until  after  the  dried  bile 
have  been  extracted  with  alcohol.  He  then  evaporates 
the  filtrate  to  dryness,  and  dissolves  in  a  small  quantity 
of  absolute  alcohol,  precipitating  by  excess  of  aether.* 
Both  these  methods  succeed  on  the  small  scale,  but  for 
the  preparation  of  large  quantities  I  prefer  the  plan 
mentioned  first. 

These  colourless  crystals  are  composed  in  the  ox 
of  the  soda  salts  of  the  two  acids  ;  they  are  exceedingly 
deliquescent,  and  therefore  very  soluble  in  water. 
They  have  a  peculiar  bitter,  sweet  taste.  They  are 
soluble  in  alcohol,  insoluble  in  aether. 

Frerichs  and  Stadeler  found  that,  if  the  pure  soda 

•  Hoppe-Seyler,  Handbiich  d.  phys.  und path,  chcmischcn  Analyse,  Berlin,  1865, 
p.  149. 


Pettenkofefs  Test.  5 

salts  of  the  bile  acids  were  acted  on  by  strong  sul- 
phuric acid,  there  was  formed  at  first  a  colourless 
mucilaginous  mass  which  dissolved  by  degrees  in  the 
cold  into  a  saffron  yellow  fluid,  with  heat  into  a  bright 
red  or  brown-red  fluid.*  These  authors  thought  this 
observation  of  much  importance,  showing  the  change 
of  bile  acid  into  bile  pigment. 

It  is  to  the  presence  of  this  'crystallised  bile'  in 
the  bile  that  this  secretion  gives  the  reaction  named 
after  Pettenkofer.f  If  to  a  watery  solution  of  the  bile 
acids  strong  sulphuric  acid  be  added,  the  bile  acids  are 
first  thrown  down,  and  then  re-dissolved  by  adding 
more  sulphuric  acid.  If  now  a  drop  of  syrup  (cane 
sugar)J  be  added  to  the  warm  solution,  the  temperature 
of  which  must  not  be  allowed  to  rise  above  70°  C.  a 
fine  purple  colour  is  developed;  compared  by  Petten- 
kofer  himself  to  a  solution  of  permanganate  of  potash. 
The  development  of  this  colour  constitutes  Pettenkofer's 
test.  The  reaction  is  given  by  glycocholic  acid,  tauro^ 
cholic  acids,  and  many  of  their  derivatives. 

Neukomm  found  that  a  watery  solution  of  the  bile 
acids,  'Afper  cent,  in  strength,  gave  a  fine  reaction:  with 
•I  per  cent,  the  colour  was  purple  red  with  a  trace  of 
violet  :  with  'O/^  per  cent,  only  a  weak  wine  red  colour; 
and  with  "01  per  cent,  only  a  yellow  fluid  which  did  not 
become  red  on  standing.  Neukomm  thinks  that  the 
reaction  becomes  much  more  delicate  if  done  in  a  por- 
celain dish  in  the  following  manner :  a  drop  of  the 
fluid  to  be  tested  is  let  fall  into  a  Berlin  dish  with 
another  drop  of  dilute  sulphuric  acid,  one  to  four,  and 
just    a  trace  of  solution   of  cane  sugar    added    to   the 

*  Frerichs  and  Stadeler,  Arch.  f.  Anat.  Phys.  u.s.w.  1856,  p.  55. 

f  Pettenkofer,  Annalcn  d.  Chetnie  u.  Pharin.  1844,  Bd.  lii.  p.  go. 

I  Jurasz  {Centralblattf.  d.  med.  Wiss.  1875,  p.  515)  finds  that  the  reaction  also 
appears  with  grape  and  fruit  sugar,  most  rapidly  of  all  with  this  last ;  slowly  with 
grape  sugar.  He  thinks  the  ordinary  reaction  due  to  the  splitting  up  of  the  cane 
sugar  by  the  sulphuric  acid  into  grape  and  fruit  sugar. 


6  Pettenkofer'' s  Test. 

whole,  and  then  it  is  rolled  about  over  the  flame  of  a 
spirit  lamp.  The  heat  used  for  the  evaporation  must 
be  small.  As  the  fluid  evaporates,  a  fine  red  purple  is 
developed.  Neukomm  says  that  in  this  way  he  has 
detected  "006  of  a  milligramme.* 

Other  modifications  of  Pettenkofer's  test  have  been 
introduced,  notably  by  Bogomoloff  and  Strassburg. 
Bogomoloff  recommends  that  the  bile  acids  be  dis- 
solved in  alcohol,  or  that  the  watery  solution  have  a 
great  excess  of  alcohol  added,  and  then  evaporated 
over  a  water-bath  in  a  porcelain  dish,  moving  the  dish 
gently  about  so  that  the  bile  acids  may  form  a  tolerably 
even  coating  over  the  dish.  A  drop,  or  two,  of  sul- 
phuric acid  is  now  let  fall  by  means  of  a  glass  rod 
upon  the  dried  bile  acids,  and  in  the  same  place  a  drop 
or  two  of  spirit.  A  number  of  colours  appear.  In  the 
centre,  the  colour  is  yellow,  then  around,  first  orange, 
then  red,  rose  red,  violet,  indigo  violet,  indigo  blue  ; 
lastly  the  whole  spot  becomes  blue.  By  this  method 
Bogomolofl"  says  he  has  detected  3  milligrammes  of 
bile  acid  in  15  CCf 

■^  Strassburg  recommends  another  way,  chiefly  for  the 
testing  of  urine.  A  little  cane  sugar  is  added  to  the 
fluid,  and  a  piece  of  filtering  paper  is  dipped  into  the 
mixture.  The  filtering  paper  is  then  dried,  and  on  it 
is  let  fall  a  drop  of  strong  sulphuric  acid  by  means  of 
glass  rod ;  in  a  quarter  of  a  minute  a  violet  colour 
appears  around  the  drop  of  acid. J  I  cannot  say  that 
I  have  found  this  a  trustworthy  modification.  A  pur- 
plish colour  may  be  seen  in  urine  from  many  persons 
not  known  to  be  seriously  disordered.  Strassburg 
says  he  has  detected  '00003  g^m.  of  bile  acid  by  this 
method. 

•  Neukomm,  Annnlcn  d.  Chcmic  und  Pharmacic,  i860,  Bd.  cxvi.  p.  30. 
f  Bogomoloff,  CcnLralblattf.  d.  vied.  Wiss.  i86g,  p.  486. 
\  SUrt-iaburg,  Arch.  f.  d.  gcs.  Pliys.  iUji,  Bd.  iv.  p.  461. 


Pettenkofer's  Test.  7 

A  red  or  purple  colour  is  given  by  many  other  bodies 
besides  the  bile  acids.  Pettenkofer  himself  noted  that 
the  reaction  appeared  with  a  solution  of  albumen,  but 
not  of  mucus  :*  an  observation  which  was  confirmed 
by  Max  Sigm.  Schultze,  who  found  that  muscular  tissue, 
voluntary  or  involuntary,  the  crystalline  lens,  the  nerve 
fibres,  and  ganglia,  showed  a  red  colour  with  sulphuric 
acid  and  sugar.  The  colour  did  not  appear  with 
tendons  or  connective  tissue,  so  that  the  tissues  rich 
in  albumen  gave  the  reaction,  but  not  those  rich  in 
gelatin. f  Beneke  has  noted  the  same  appearance  with 
chemically  pure  oleic  acid,  and  with  pure  aether,  and 
also  under  certain  concentrations  with  cholestearin.J 
Schneider,  too,  finds  that  morphia  and  cadeia  give 
the  same  reaction,  but  not  narcotin,  nor  narcein, 
quinine,  strychnia,  brucia,  atropia,  colchicin,  emetia, 
or  picrotoxin.§  The  reaction  is  said  also  to  appear 
with  amylic  alcohol. 

Koschlakoff  and  Bogomoloff,  noting  this  false  Pet- 
tenkofer's  reaction  with  albumen  and  other  bodies,  say 
that  the  spectrum  affords  a  sure  means  of  diagnosis. 
The  fluid  of  Pettenkofer's  reaction  is  so  deeply 
coloured  that  it  must  be  diluted  before  light  can  pass 
through.  This  dilution  is  best  done  with  acetic  acid, 
as  water  throws  down  a  violet  precipitate.  This  fluid 
in  the  spectroscope  shows  with  moderate  concentration 
four  absorption  bands  ;  the  largest  and  most  intensely 
marked,  shows  itself  in  E  and  a  little  to  the  left.  The 
other  in  F.      The  third  between   D  and  E,  nearer  to 


*  Pettenkofer,  he.  cit. 

f  Max.  Sigm.  Schultze,  Annalen  d.  Chemie  u,  Pharmacie,  1849,  Bd.  Ixxi.  p.  273. 
Like  observations  have  been  made  on  the  tissues  of  invertebrate  animals  by 
Friedrich  Will  {Arch.  f.  Anat.  Phys.  ii.s.w.  1848,  p.  502),  and  Voit  {Zeitschrift 
f.  wlss.  Zoologie,  i860,  Bd.  x.  p.  470.) 

X  Beneke,  Stiidicn  ueber  das  Vorkommen,  die  Vcrbreitung  tmd  die  Function  von 
Gallenbestandthcilen,  u.s.w.  Giessen,  1862,  pp.  35  et  seq. 

§  Schneider,  Annalen  der  Physik  und  Chemie,  1872,  Bd.  cxlvii.  p.  128. 


8  Spectrum  of  Pettenkofer^s  Test. 

D.  The  fourth  near  D.  If  the  fluid  be  more  dilute, 
the  bands  in  E  are  well  seen,  between  D  and  E 
much  less  marked,  and  in  D  and  F  very  weak.  With 
high  concentration,  the  absorption  bands  in  E  and 
between  D  and  E  unite  in  one  plainly  marked  band. 
In  F  there  is  a  well-marked  band.  In  D  the  bands  are 
always  well  marked. 

These  observers  also  remark  that  the  fluid  of  Petten- 
kofer's  reaction  shows  a  fluorescence,  if  well  diluted 
with  dilute  acetic  acid  ;  it  is  green  by  reflected  light ; 
cherry  red  by  transmitted  light.*  This  observation 
has  been  repeated  by  Schenk  ;  and  he  also  finds  ab- 
sorption bands  in  the  fluid  of  Pettenkofer's  test,  but 
they  are  somewhat  different  in  place  and  number  from 
those  noted  by  Koschlakoff  and  Bogomoloff.  If  the 
solution  be  dilute  there  is  seen  at  F  an  absorption  band 
Vv'hich  fills  about  half  the  space  between  E  and  F ; 
there  is  another  band  at  the  line  E  between  D  and  E, 
and  it  fills  half  of  this  space.  But  if  the  solution  be 
concentrated  there  is  only  seen  one  band  between  D 
and  E.t 

Dalton  also  found  absorption  bands  in  the  alcoholic 
solution  of  Pettenkofer's  reaction  ;  two  wide  and  dark 
bands,  one   at  E,  from  D  50  E  to  E  25  F  ;    the  other  at 

F,  from  E  60  F  to  F  15  G,  the  spectrum  ending  about 

G.  A  band  at  D  was  also  frequently  seen. 

The  solution  in  alcohol  of  the  bile  acids  shows  a 
spectrum  in  which  the  bands  at  E  and  F  are  visible  and 
often  also  the  band  at  D.  It  makes  a  great  difference 
if  alcohol  or  water  be  used  as  a  solvent :  the  watery 
solution  gives  only  one  band  at  E.  Beyond  the  bands 
the  spectrum  is  dim. 

•  Koschlakoff  and  Bogomoloff,  Cenlralblattf.  d.  vied.  Wiss.  1868,  p.  529. 

f  Schenk,  Analomisch-physiologisclie  Untcysuchungcn,  Wien,  1872,  p.  47.  I 
have  not  been  able  to  find  the  observations  of  Waterman,  as  quoted  by  Schenk. 
On  the  contrary,  Waterman  says  (New  York  Medical  Record,  1871-2,  Vol.  vi.  p. 
436.)  that  normal  bile  is  nearly  devoid  of  the  pov.cr  of  affecting  the  spectrur^ 


Glycocholic  Acid.  g 

There  is  no  difference  between  the  spectra  of  glyco- 
cholate  or  taurocholate  of  soda. 

Dalton  thinks  that  the  characters  of  the  spectrum  of 
the  fluid  of  Pettenkofer's  reaction  may  be  used  to  dis- 
tinguish it  from  the  red  fluids  obtained  by  a  like  re- 
action on  morphia,  albumen,  and  the  like.  He  finds 
that  the  opium  alkaloids  give  a  band  at  E,  but  it  is 
somewhat  indistinct  and  disappears  on  dilution.  Albu- 
men gives  a  single  band  in  the  space  between  E  and  F, 
the  edges  are  not  well  defined  and  the  spectrum  beyond 
is  dim.*  Bogomoloff  finds  that  the  spectrum  of  oil 
treated  with  Pettenkofer's  method  gives  two  bands  : 
one,  more  intense  than  the  other,  between  D  and  E, 
nearer  to  D  :  the  other  on  the  left  of  D.f 

Glycocholic  acid.  For  the  knowledge  of  this  acid  we  are 
indebted  to  Strecker,  and  according  to  his  advice  it  is 
prepared  by  dissolving  the  crystallised  bile  from  ox-bile  in 
water  and  then  throwing  down  the  pure  acid  with  dilute 
sulphuric  acid.  The  addition  of  acid  must  be  stopped 
as  soon  as  a  slight  precipitate  be  formed.  After  a  few 
hours  the  fluid  is  found  full  of  stellate  needles,  which 
should  be  collected  on  a  filter,  washed  with  water, 
and  pressed. 

It  is  not  needful,  however,  to  use  crystallised  bile  in 
the  first  instance  ;  the  acid  may  be  thrown  down  from 
bile  purified  according  to  Theyer  and  Schlosser's 
method, J  and  the  precipitate  thrown  into  aether 
forms  a  heap  of  stellate  crystals. § 

Another  way  is'  to  precipitate  a  solution  of  crystal- 
lised bile  with  neutral  acetate  of  lead.  After  complete 
precipitation  with  this  salt,  a  second  precipitation  may 
be    made   with   basic    acetate   of  lead   to  throw  down 


*  Dalton,  New  York  Medical  jfournal,  1874,  Vol.  xix.  p.  589. 

f  Bogomoloff,  Cc}itralblattf.  d,  med.  Wiss.  1869,  P-  484- 

J  Theyer  and  Schlosser,  Anualen  d.  Cheinie  und  Pharinacie,  1843,  Bd.  xlviii.  p.  77. 

§  Adolph  Strecker,  ibid.  1848,  Bd.  Ixv.  p.  g. 


lo  Glycocholic  Acid. 

taurocholate  of  lead.  The  precipitates  are  the  lead  salts 
of  the  two  bile  acids,  glycocholic  and  taurocholic  acid. 
The  precipitates  must  be  dissolved  in  hot  alcohol,  sul- 
phuretted hydrogen  passed  through,  and  then  water 
added  to  the  concentrated  alcoholic  solution,  which 
throws  down  the  glycocholic  acid. 

Gorup-Besanez  evaporates  ox-gall  almost  to  dryness 
in  a  water  bath,  and  then  extracts  with  alcohol  of  go. 
per  cent.  The  alcohol  is  distilled  or  driven  off  from  the 
filtered  solution,  the  residue  is  diluted  with  water  and 
milk  of  lime  is  added,  to  throw  down  the  pigment 
which  combines  with  the  lime.  The  somewhat  yellow 
coloured  filtrate  is  now  first  neutralised  with  sulphuric 
acid,  and  then  just  enough  added  to  throw  down  the 
glycocholic  acid,  but  all  excess  should  be  avoided.  In 
a  few  hours  the  whole  becomes  a  mass  of  crystals 
which  must  be  filtered,  washed,  and  pressed.* 

A  quicker  way  of  preparing  pure  glycocholic  acid  is 
recommended  by  Hiifner.  Fresh  ox  bile  is  put  into  a 
narrow  cylindrical  glass  and  aether  poured  on  to  the 
surface  of  the  bile  ;  then  a  strong  mineral  acid  is  added 
to  the  bile  so  as  to  throw  down  the  bile  acids.  First 
a  milky  precipitate  is  formed  which  later  on  becomes 
crystalline,  sometimes  so  rapidly  that  the  whole  mass 
becomes  solid ;  the  aether  turns  of  a  yellow  or  brown 
colour,  but  after  standing  some  time  becomes  purple  or 
violet.  The  mass  of  crystals  must  be  separated  from 
the  aether  and  shaken  up  forcibly  in  a  stoppered  vessel, 
then  put  into  a  filter  and  washed  on  the  filter  with 
cold-water  until  the  filtrate  cease  to  be  of  a  green 
colour.  This  filtrate  contains  the  taurocholic  acid 
which  is  readil}^  soluble  in  water.  The  glycocholic 
acid  is  not  soluble  in  cold,  but  readily  in  hot,  water  : 
to  purify  the  mass  on  the  filter  it  must  be  dissolved 

*  Gorup-Besanez,  Annalcn  dcr  Chcinic  unci  Pharm.  1871,  Bd.  clvii.  p.  286. 


Glycocholic  Acid.  ii 

in   boiling  water,   rapidly  filtered,   and   when  cold  the 
acid  crystallises  out  in  purity.* 

Our  knowledge  of  the  composition  of  glycocholic  acid 
is  entirely  due  to  the  labours  of  Strecker.  He  found 
that  if  glycocholic  acid  be  boiled  for  many  hours-,  about 
24,  with  caustic  baryta,  that  the  glycocholic  acid  is 
completely  decomposed  into  two  bodies  :  cholalic  acid 
and  glycocoll  if 


Cholalic  acid.                Glycocoll. 

Glycocholic  acid. 

(324^4006      4.      aNH^O^  — 

H'-O 

=    C^'^H^NO'^ 

or  in  the  old  notation  : 

Cholalic  acid.               Glycocoll. 

Glycocholic  acid. 

Q^YiiOQio     _|.     C^NH^O^  —  2HO    =    C^^H^^NCP 

A  like  decomposition  takes  place  if  glycocholic  acid 
be  boiled  with  acids,  especially  hydrochloric  acid :  a 
precipitate  is  thrown  down  consisting  of  hydrochlorate 
of  glycocoll,  (glycin  or  glycocine).  If  this  body  be 
dissolved  in  water,  and  heated  with  oxyde  of  lead,  the 
chloride  of  lead  separated,  and  the  superabundant  lead 
removed  with  sulphuretted  hydrogen,  the  filtrate  may  be 
evaporated  for  crystallisation.  Glycocoll  is  a  crystalline 
body;  it  forms  large  rhombohedra  which  are  easily  solu- 
ble in  water,  very  little  in  hot  alcohol,  insoluble  in  cold 
alcohol  and  in  sether.  It  is  not  needful  to  go  deeply 
into  the  chemistry  of  this  body  in  this  work ;  but  it  is 
well  to  say  that  it  is  an  amide  uniting  with  both  acids 
and  bases :  according  to  its  composition  it  would  be 
amido-acetic  acid.  It  has  been  synthetically  made  by 
Perkin  and  Duppa  from  mono-brom- acetic  acid,  J  and 
by  Cahours§  from  mono-chlor-acetic  acid  : 

Glycocoll. 

OH^'CIO^  +  2HW  =  OW  (NH^)  O  (OH)   -f  NHCl 

*  Hiifner,  Journal  f.  fvakt.  Chemie,  1874,  Bd.  cxviii.  p.  267. 
t  Adolph  Strecker,  Annalen  d.  Chemie  tmd  Pharmacie,  1848,  Bd.  Ixvii.  pp.  2 
et  seq. 

X  Perkin  and  Duppa,  Phil.  Mag.  1857,  Vol.  xiv.  p.  217. 
§  Cahours,  Comptes  rcndiis,  1858,  t.  xlvi.  p.  1044. 


12  Glycocholic  Acid. 

It  may  be  prepared  from  gluten,  and  even  in  small 
amount  from  albuminous  bodies.  It  is  important  to 
the  physiological  chemist  because  it  enters  into  the 
composition  of  hippuric  acid  as  well  as  of  the  bile  acids. 
Hippuric  acid  is  benzoic  acid  plus  glycocoll.  Hoppe- 
Seyler  recommends  glycocoll  to  be  prepared  by  boiling 
h3'drochloric  acid  with  hippuric  acid.*  It  has  no  in- 
fluence on  polarised  light. 

Glycocholic  acid  has  not  yet  been  made  directly  from 
a  combination  of  cholalic  acid  and  glycocoll.  Glyco- 
cholic acid  may  be  looked  upon  as  a  chol-amide  acetic 

acid : 

C2iH38   (C^H^    (NH^)    O)    OMq 

The  crystals  of  glycocholic  acid  are  fine  white  needles, 
which  even  when  looked  at  with  a  microscope  magnify- 
ing 300  times,  scarcely  show  a  diameter. 

Glycocholic  acid  is  but  slightly  soluble  in  water ; 
1000  parts  of  cold  water  dissolve  3*3  of  the  acid  ;  and 
the  same  parts  of  boiling  water  8*3.  The  solution  is 
sweet  and  somewhat  bitter  to  the  taste ;  it  reddens 
litmus  and  shows  no  reaction  with  acids,  acetate  of 
lead,  corrosive  sublimate,  or  nitrate  of  silver ;  sub-ace- 
tate of  lead  causes  a  slight  precipitate. 

The  acid  is  very  soluble  in  alcohol ;  and  if  it  be 
heated  in  a  water  bath  becomes  a  syrupy,  later  on,  a 
resinous  mass,  from  which  crystals  cannot  again  be 
obtained. 

In  aether,  glycocholic  acid  is  but  slightly  soluble ; 
but  much  ffither  must  be  added  to  a  concentrated 
alcoholic  solution  before  it  be  even  partly  thrown 
down. 

Concentrated  sulphuric,  hydrochloric,  and  acetic 
acids  dissolve  glycocholic  acid.     Alkalies  readily  dis- 

*  Hoppc-Seyler,  Ilniulb.  d.  phys.  uixJ  path.  cJuiii.  Analyse,  Berlin,  1865,  p.  124. 


Salts  of  Glycocholic  Acid.  13 

solve  it.     It  expels  the  carbonic  acid  from  the  alkaline 
carbonates. 

The  combination  of  glycocholic  acid  with  soda  is  that 
which  is  the  most  important,  inasmuch  as  this  is  the 
salt  which  is  found  in  the  bile.  It  crystallises  in  white 
needles,  just  like  crystallised  bile.  It  is  very  soluble 
in  water,  less  so  in  absolute  alcohol.  1000  parts  of 
alcohol  dissolve  at  15°  C.  39  parts  of  glycocholate  of 
soda. 

There  are  also  glycocholates  of  potash,  ammonia, 
and  baryta,  all  soluble  in  water. 

De  I'Arbre  finds  that  the  bile  acids  unite  and  form 
crystals  with  alkaloids,  such  as  strychnine,  brucine, 
morphia,*  &c. 

Hoppe-Seyler  has  found  that  the  bile  acids  and  their 
derivatives  have  a  marked  influence  on  polarised  light. 
Glycocholic  acid  has  a  dextro-rotatory  power  for  red 
light  of  +27°  '22:  for  yellow  light  +29°  '93  ;  and  it 
is  inferred  for  sun  light  +36°  -15.  The  rotatory  action 
is  the  same  whether  the  acid  be  in  combination  with  a 
base  or  not.t 

Taiirocholic  Acid. — Strecker  showed  that  the  precipi- 
tate thrown  down  by  sub-acetate  of  lead,  after  the 
precipitate  thrown  down  by  acetate  of  lead  had  been 
separated,  contained  an  acid  different  from  glycocho- 
lic, inasmuch  as  sulphur,  as  well  as  nitrogen,  entered 
into  its  composition.  He  was,  however,  unable  to 
separate  the  glycocholate  of  lead  from  the  taurocholate ; 
he  therefore  subjected  the  lead  precipitate  to  the  same 
process,  boiling  with  baryta,  that  was  so  fruitful  in  the 
decomposition  of  glycocholic  acid.  A  like  decomposi- 
tion  did  indeed  set  in  ;    with  cholalic  acid,  two  bodies, 

*  De  I'Arbre,  Chem.  Centralblatt,  1872,  p.  231.  See  also  Malinin,  Centralblatt 
f.  d.  med.  Wiss.  1868,  p.  370. 

t  Hoppe-Seyler,  Arch.  f.  path.  Anat.  1858,  Bd.  xv.  p.  130.  More  elaborate 
observations  by  Hoppe-Seyler  on  this  same  subject  will  be  found  in  the  Jouynal  f. 
prakt.  Chemie,  1863,  Bd.  Ixxxix.  p..  257. 


14  Taurocholic  Acid. 

taurin  and  glycocoll,  were  formed,  instead  of  one,  gly- 
cocoll.  These  two  were  readily  separated  by  means 
of  alcohol  containing  hydrochloric  acid,  in  which  gly- 
cocoll is  readily  soluble,  while  taurin  is  but  very  slightly 
taken  up  by  it.*  Taurocholic  acid  is  therefore  a  com- 
pound of  taurin  and  cholalic  acid  : 

Cholalic  Acid.  Taurin.  Water.         Taurocholic  Acid. 

or  in  the  old  notation  : 

(348^40010    +    C^R'NC'S^    +    2  HO   =   C^^H^NO^^S^ 

Of  taurin  it  will  be  enough  to  say  that  its  formula 
was  first  accurately  given  by  Redtenbacher,*!"  and  a 
rational  formula  by  Kolbe.J  It  is  amido-is^thionic 
(gethyl  sulphuric)  acid.  It  may  be  formed  synthetically 
by  heating  the  ammoniacal  salt  of  issethionic  acid  to 
210°  C.§  or  else  by  the  action  of  ammonia  upon  the 
chlorsethyl  sulphate  of  silver. 

Taurin  is  a  crystalline  body,  forming  colourless  prisms, 
quadrate,  or  oftener  hexagonal,  with  four-sided  pyra- 
mids at  each  end.  Its  solution  is  neutral  and  it  unites 
with  neither  acids  nor  bases.  This  body  is  one  of  the 
richest  in  sulphur  of  those  found  in  the  ceconomy.  It 
has  no  action  on  polarised  light.  || 

Taurocholic  acid  may  be  obtained  by  decomposing 
its  lead  salt  with  sulphuretted  hydrogen,  filtering,  and 
evaporating  at  a  low  temperature.  It  has  not  yet  been 
seen  in  crystals  \%  it  is,  reversing  the  property  of 
glycocholic  acid,  readily  soluble  in  water.  The  solution 
is  acid    and    soon  decomposes,   even  on  boiling.      By 


*  Strecker,  Annalcn  d.  Chemie  u.  Pharinacic,  1848,  Bd.  Ixvii.  p.  31. 
f  Redtenbacher,  ibid.  1846,  Bd.  Ivii.  p.  170. 

*  Kolbc,  ibid.  1859,  Bd.  cxii.  p.  241,  and  1862,  Bd.  cxxii.  p.  33. 
§  Strecker,  ibid.  1854,  Bd.  xci.  p.  loi. 

II  Hoppe-Seyler,  Arch.f.  path.  Anat.  1858,  Bd.  xv.  p.  132. 

IT  J.  Parke,  Hoppe-Seyler's  Med.  chetn.  Unlcrsuchuiigcn,  Berlin,  1866,  p.  160. 


Salts  of  Taurocholic  Acid.  15 

boiling  with  acids  or  alkalies  it  is  decomposed  into 
taurin  and  cholalic  acid. 

Strecker  describes  the  alkaline  salts  of  taurocholic 
acid  as  very  soluble  in  water  and  spirit,  but  insoluble 
in  aether.  They  have  no  action  on  litmus  paper. 
Exposed  to  moist  air,  they  increase  considerably  in 
weight  but  do  not  deliquesce.  When  heated  upon  pla- 
tinum foil,  the  salt  first  melts,  then  throws  off  bubbles, 
and  burns,  leaving  behind  it  an  ash.  The  watery  solu- 
tion tastes  sweet  with  a  bitter  after-taste.  The  acid  is 
not  thrown  down  by  acids,  even  by  concentrated  sul- 
phuric acid.  If  boiled  with  acids,  oily  drops  of  cho- 
loidic  acid  are  thrown  down,  and  the  fluid  retains 
taurin  in  solution.  By  adding  concentrated  solution  of 
potash  to  a  watery  solution  of  an  alkaline  taurocholate-, 
the  potash  takes  over  completely  the  taurocholate  to 
itself.  In  the  same  way  the  taurocholate  drives  out 
the  carbonic  acid  of  an  alkaline  carbonate  ;  but  has  no 
influence  on  a  sulphate  or  chloride.  Carbonic  acid 
does  not  unite  with  the  alkali  of  any  alkaline  tauro- 
cholate in  alcoholic  solution.  With  lime,  baryta,  and 
magnesia  salts  there  is  no  precipitate,  nor  even  with 
ammonia.  With  neutral  acetate  of  lead  there  is  no 
precipitate,  but  white  flakes  are  thrown  down  by  the 
sub-acetate.  These  are  dissolved  by  heat,  and  again 
thrown  down  by  cooling,  and  are  also  soluble  in  a 
great  excess  of  sub-acetate  of  lead.  After  complete 
precipitation  with  sub-acetate  of  lead,  there  appears  a 
fresh  precipitate  with  ammonia. 

The  watery  and  alcoholic  solutions  of  taurocholates 
may  be  evaporated  in  a  water  bath  without  under- 
going change ;  nor  are  they,  if  pure,  decomposed  by 
long  keeping.  The  solution  of  the  free  acid  cannot 
be  evaporated  to  dryness  without  decomposition. 

In  watery  solutions  of  alkaline  taurocholates  there 
is  no    precipitate  with   acetate  of  copper,   but  a  little 


1 6  Salts  of  TanrochoUc  Acid. 

ammonia  throws  down  bluish  white  flakes  soluble  in 
excess :  nitrate  of  silver  gives  no  precipitate,  even 
with  ammonia,  and  on  boiling,  a  part  of  the  silver 
is  reduced.  Perchloride  of  iron  at  first  gives  a  pre- 
cipitate soluble  in  excess.  Perchloride  of  mercury 
gives  no  precipitate,  but  the  nitrate  of  mercury  and 
chloride  of  zinc  throw  down  white  flakes.  Taurocho- 
lates  give  Pettenkofer's  reaction.* 

Hoppe-Seyler  has  found  that  the  dextro-rotatory 
power  of  taurocholic  acid  for  red  light  is  +  24°  '92  ;  for 
yellow  +  25°  -28. t 

The  bile  acids  are  not  the  same  throughout  the  ver- 
tebrate sub-kingdom.  The  bile  of  the  lower  animals 
has  been  investigated  by  several  chemists,  chiefly  by 
Strecker.  It  would  seem  probable  that  the  nitrogenous 
bases  of  the  bile  acids  are  always  the  same,  glycocoll 
and  taurin,  while  the  acid  with  which  they  are  com- 
bined is  the  body  which  varies. 

Strecker  finds  the  bile  acid  of  dogs  to  be  entirely 
taurocholic  without  a  trace  of  glycocholic  :J  but  Dr. 
George  Scott  found  a  glycocholate  in  the  bile  of  a  dog, 
sometimes  as  much  as  one-third  of  the  whole  bile  acid 
salts. §  Hoppe-Seyler  endorses  Strecker's  statement, || 
which  appears  to  be  generally  received. 

Thenard  says  of  the  bile  of  the  pig,  that,  unlike  the 
bile  of  the  ox,  it  is  a  true  soap  :  from  it  he  could  obtain 
no  picromel.^ 

■  Strecker  and  Gundelach  found  in  the  bile  of  pigs,  as 
its  chief  constituent,  an  acid  nitrogenous  but  free    from 

*  Strecker,  Annalcn  d.  Chemic  utid  Pliannncic,  1848,  Bd.  Ixvii.  p.  46. 
f  Hoppe-Seyler,  Arch./,  path.  Anat.  1858,  Bd.  xv.  p.  132. 
J  Strecker,  Annalcn  d.  Chcmie  u.  Pharinacic,  1849,  Bd.  Ixx.  p.  178. 
§  George  Scott,  Beale's  Archives  0/ Medicine,  1859,  vol.  i.  p.  217. 
II  Hoppe-Seyler,  Phys.  Chcmie,  Berlin,  1878,  p.  289. 

II  Thenard,  Mimoires  de  physique  ct  dc  chemic  dc  la  Societe  d'Arcucil,  1807,  t.  i. 
r-  49- 


Hyocholic  Acid.  17 

sulphur,  which  they  called  hyocholic  acid.*  It  differs 
greatly  from  the  glycocholic  acid  of  oxen.  It  is  insolu- 
ble in  water,  and  forms  with  lime  and  baryta  a  salt 
either  insoluble  or  hardly  soluble  in  water.  The  alka- 
line salts  are  thrown  down  out  of  their  watery  solution 
by  chloride  of  sodium,  chloride  of  ammonium,  or  alkaline 
sulphates,  a  means  by  which  the  acid  may  be  had  in 
purity:  the  formula  for  the  salts  is  C^^H^^nO^"  +  MO ;  for 
the  acid  C^^H^^nHO'".  The  acids  make  up  JSper  cent. 
of  the  solids  of  pig's  bile  ;  and  of  this  about  ■0'47  per 
cent,  is  sulphur.  There  is,  therefore,  probably  a  bile 
acid  which  has  the  same  relation  to  hyocholic  acid,  as 
taurocholic  has  to  glycocholic. "j" 

Hoppe-Seyler  thinks  that  the  acids  of  pig's  bile  have 
probably  a  more  complicated  composition  than  the  gly- 
cocholic and  taurocholic  acid  of  other  mammals,  as  he 
finds  they  have  considerable  differences  in  their  influence 
on  the  polarised  beam,  differences  which  are  not  always 
constant.  Hoppe-Seyler  gives  +  2°  for  hyoglycocholic 
acid  in  yellow  light,  and  -f-  23*62°  for  hyocholoidic  acid, 
an  acid  formed  by  the  boiling  of  hyoglycocholic  acid 
with  hydrochloric  acid.  J 

The  bile  of  a  female  kangaroo  (Halniaturus),  was 
found  by  Schlossberger  to  be  neutral,  and  to  give  a 
well-marked  Pettenkofer's  reaction :  there  were  14*13 
per  cent,  of  solids,  distributed  as  follows  : 

Mucus  and  Colouring  Matters    .     .  4*34. 

Cholestearin  and  Fat I'Gq. 

Bile  Acid  Salts 7*59. 

Loss  and  other  Salts I*li. 

Very  little  sulphur  {2'4'j  per  cent.)  was  found,  so  that 
the  bile  of  the  kangaroo  is  one  of  the  poorest  in   tauro- 

*  Strecker  and   Gundelach,  Annalen  d.   Chemie   mid  Pharmacie,  1847,  B^-  1^"- 
p.  205. 

f  Strecker,  ibid.  1849,  Bd.  Ixx.  p.  179. 

I  Hoppe-Seyler,  Arch.  f.  path.  Anat,  1858,  Bd.  xv.  p.  139. 

C 


1 8  Chenocholalic  Acid. 

cholic  acid  yet  examined.     The  bile  of  the  pig,  however, 
contains  less  sulphur.* 

Tiedemann  and  Gmelin  are  said  to  be  the  first  who 
investigated  the  bile  of  geese,  though  from  the  imperfect 
state  of  the  chemistry  of  the  bile  at  that  time  but  little 
was  added  to  knowledge  by  their  observations. f  Marsson 
later  on  took  up  the  work,  and  found  that  the  bile  in 
the  gall  bladders  of  geese  fed  on  oats  contained  about 
20  per  cent,  of  solid  matter.  He  found  sulphur  very 
abundant  in  this  bile  ;  and  thought  that  it  might  turn 
out  to  contain  a  new  acid,  nearly  allied  to  Strecker's 
eholeic  acid,  and  to  this  new  acid  he  gave  the  pro- 
visional name  of  chenocholeic  acid.  It  gives  Petten- 
kofer's  reaction. J 

Heintz  and  Wislicenus  found  a  peculiar  acid,  as 
Marsson  did,  in  the  bile  of  geese,  but  they  carried  their 
investigations  far  wider.  They  found  the  cholalic  acid 
to  be  in  no  way  like  the  ordinary  cholalic  acid  of  oxen,  or 
the  hyocholalic  acid  of  pigs.  Even  the  shape  of  the 
crystals  of  the  soda  salt  is  different.  The  amount  of 
carbon  is  much  greater,  that  of  oxygen  much  less,  than  in 
the  ordinary  bile  acid,  but  its  formula  is  homologous  with 
that  of  hyocholalic  acid  ;  the  formula  of  chenocholalic 
acid  is  C^^H^^O^  while  that  of  hyocholahc  acid  is  C5°H^°0^ 

In  the  bile  of  geese  these  observers  have  also  found 
another  acid,  containing  sulphur,  analogous  to  tauro- 
cholic  acid,  and  which  they  call  tauro-chenocholic  acid, 
as  in  it  chenocholalic  acid  is  combined  with  taurin.  Its 
formula  is  C5«H'»^NS^0'^§ 

Berzelius  seems  to  have  been  the  first  to  examine 


*  Schlossberger,  Annalcn  d.  Chcmie  u.  Phavin.  1859,  Bd.  ex.  p.  244. 

f  Tiedemann  and  Gmelin,  Die  Vcrdauung,  Heidelberg  and  Leipzig,  1827,  Bd. 
ii.  p.  145. 

■J:  T.  Marsson,  The  Chemist,  1849-50,  vol.  i.  new  series,  p.  64,  abstract  from 
Arch,  der  Pharmacie,  2.  Reihe,  Bd.  Iviii.  p.  138. 

§  Heintz  and  Wislicenus,  Poggendorfrs/l««rt/c)i  d,  Phys.  und  Chemie,  1859,  Bd. 
cviii.  p.  547. 


Bile  of  Snakes  and  Fish.  ig 

the  bile  of  snakes,  of  a  coluber  and  a  python  ;*  though  the 
results  of  his  observations  are  not  now-a-days  of  any 
value  to  the  physiologist.  Later  on  Schlieper  examined 
the  bile  from  the  gall  bladder  of  a  Boa  annaconda,  and 
found  the  ashes  after  examination  to  consist  chiefly  of 
sulphate  of  soda,  and  that  the  dry  residue  of  the  bile 
held  about  6  per  cent,  of  sulphur. f  Schlossberger,  in 
the  bile  of  a  python  tigris,  found  the  same  percentage  of 
sulphur,  and  concludes  that  in  this  kind  of  snake  the 
only  bile  acid  present  is  the  taurocholic  in  combination 
with  soda. J 

In  the  bile  of  salt-water  fish  there  is  seen  an  ex- 
ception to  the  general  rule  that  the  bile  acids  are  in 
combination  with  soda.  Strecker  found  the  acid  to  be 
chiefly  taurocholic,  with  very  small  traces,  if  any,  of 
glycocholic  acid.  In  the  bile  of  the  cod  {Gadus 
morrhua)  and  of  the  turbot  {Pleuronectes  maximus  or 
Rhombus  maximus)  the  chief  constituent  was  taurocho- 
late  of  potash,  while  the  bile  of  fresh  water  fish,  such 
as  the  pike  {Esox  lucius)  and  the  perch  {Perca  jluvi- 
atilis)  held  much  more  soda,  combined  in  the  bile  of 
the  pike  with  glycocholic  acid,§ 

The  bile  of  a  species  of  Silurus,  taken  from  a  speci- 
men weighing  go  pounds,  Schlossberger  found  neutral 
and  showing  a  few  epithelium  cells.  It  contained  5*52 
per  cent,  of  solids,  composed  of  3 '63  of  bile  acid  salts, 
•23  of  fat  and  i'48  of  mucus  and  pigment.  The  salts 
contained  a  large  amount  of  sulphur ;  so  that  in  this 
case  also  the  bile  acid  was  inferred  to  be  chiefly  tauro-- 
cholic,  with  a  small  amount  of  glycocholic  acid.|| 

Scherer  found  in  the  bile   of  a  sturgeon  both  glyco- 


*  Berzelius,  Poggendorff's  Annalen  d.  Physik  und  Cheinie,  1830,  Bd.  xviii.  p.  87. 

f  Schlieper,  Annalen  d.  Chemie  und  Pharniacie,  1846,  Bd,  Ix.  p.  109. 

X  Schlossberger,  ibid.  1857,  Bd.  cii.  p.  91. 

§  Strecker,  ibid.  1849,  Bd.  Ixx.  p.  i6g. 

II  Schlossberger,  ibid.  1858,  Bd.  cviii.  p.  66. 

02 


20  Sulphur  of  the  Bile. 

cholic  and  taurocholic  acids.*      It  gave  a  well-marked 
Pettenkofer's  reaction. 

The  bile  contains  but  very  little  sulphur  as  sulphuric 
acid  ;  and  so  the  amount  of  sulphur  present  becomes 
a  means  for  very  nearly  estimating  the  amount  of 
taurocholic  acid.  Advantage  has  been  taken  of  this 
by  several  chemists  in  analysing  the  bile  ;  but  unfortu- 
nately the  later-made  experiments  vary  much  from 
those  that  are  earlier.  For  example,  A.  Bensch  has 
found  the  following  amounts  of  sulphur  in  the  bile  of 
different  animals  :"|* 

In  100  Parts. 

Oxen 3-39    —     378. 

Calf,  (before  weaning-) .     .  4"88. 

Sheep 5'7i. 

Goat 5  "20. 

Pig-,  (3  analyses)      .     .     .  0*30.  0"32.  0'36. 

Bear 575. 

Dog- 6-21. 

Wolf. 5-03. 

Fox.  '. 5*96. 

Domestic  Fowl A'90. 

Fish  of  different  kinds  .     .  S"52.  5*58. 

It  has  just  been  said  that  Schlieper  and  Schlossberger 
found  6  per  cent,  of  sulphur  in  the  bile  of  a  boa  and  python 
respectively,  and  that  Scherer  and  Schlossberger  found 
the  bile  acids  of  fish  to  be  almost  entirely  made  up  of 
taurocholic  acid. 

Kiilz,  on  the  other  hand,  using  Carius'  method  of 
estimating  the  sulphur,  finds  as  follows  :J 

Per  Cent. 

Bile  of  Sheep 'id>g. 

,,      Man -136. 

,,       Swine '125. 

,,      Calves "125. 

,,      Oxen -100. 

•  Scherer,  Vcrhandlungcn  d.  phys.-mcd.  Gcscllschaft  in  Wnrzburg,  1857,  Bd.  vii. 
p.  269. 

t  Bensch,  Annalcn  d.  Cheinic  n.  Pharm.  1848,  Bd.  Ixv.  p.  194. 
X  Ki'ilz,  Arch.f.  Anat.  Pliys.  u.  s.  w.  1872,  p.  106. 


Derivatives  of  the  Bile  Acids.  21 

Salkowski  very  properly  criticises  these  results.*  A 
very  small  amount  of  bile  was  used  for  each  analysis, 
a  few  milligrammes  of  sulphates  only  being  obtained ; 
and  in  this  way  a  large  error  may  creep  in  if  the  results 
be  multiplied. 

Kunkel  also  gives  'i  grm.  in  100  C.C.  of  bile  as  the 
average  for  a  dog.t 

Derivatives  of  the  Bile  Acids. 

Cholalic  acid,  as  described  above,  is  a  product  of  the 
decomposition  of  both  glycocholic  and  taurocholic  acid. 
It  is  the  non-nitrogenous  acid  which  is  common  to 
both,  and,  by  combining  with  the  glycocoll  and  taurin, 
forms  the  special  acids  of  the  bile. 

Cholalic  acid  is  formed  by  the  decomposition  of  the  bile 
acids  by  acids,  alkalies,  or  fermentation.  Strecker  made  it 
by  long  boiling,  of  the  bile  acid  salts  with  baryta.  The  so- 
lution, when  allowed  to  cool,  gives  a  crystalline  mixture 
of  hydrate  of  baryta  and  cholalate  of  baryta.  This 
is  thrown  on  a  filter,  washed  with  a  little  boiling 
water,  and  then  thrown  into  water  acidulated  with 
hydrochloric  acid.  The  cholalic  acid  separates  as  a 
resinous  body,  and  the  solution  only  holds  chloride  of 
barium.  The  fluid,  from  which  the  cholalate  of  baryta 
was  filtered  off,  is  mixed  with  the  washings,  and  carbonic 
acid  passed  through,  by  means  of  which  the  baryta  is 
precipitated  as  far  as  may  be.  The  fluid  is  then  heated 
to  boiling,  filtered  from  the  carbonate  of  baryta,  and  the 
cholalic  acid  set  free  from  the  baryta  by  means  of  hydro- 
chloric acid.  A  small  part  of  the  cholalic  acid  remains 
in  the  carbonate  of  baryta  and  may  be  got  by  treat- 
ing it  with  carbonate  of  ammonia,  and  then  expelling 
the  cholalic  acid  with  a  stronger  acid.  The  cholalic 
acid  is  thus   obtained  in  three  different  fluids.     This  is 

*  Salkowski,  Centralblatt  f.  d.  med  Wiss.  1872.  p.  885. 
f  Kunkel,  Arch.f.  d.  ges.  Phys.  1877,  B^-  ^i^-  P-  345- 


22  Cholalic  A  cid. 

the  method  recommended  by  Strecker.*  Hoppe-Seyler 
says  that  the  bile  should  be  boiled  for  12  or  24  hours 
with  strong  potash  solution,  or  baryta  solution  satu- 
rated when  hot.  The  solution  should  be  thrown  down 
with  hydrochloric  acid,  washed  with  water,  dissolved 
in  a  little  alkali-solution,  sether  added,  precipitated 
afresh  with  hydrochloric  acid,  and  then  allowed  to  stand 
for  several  days.  By  the  addition  of  sether  the  cholalic 
acid  is  obtained  in  crystals.  The  asther  is  poured  off, 
the  mass  pressed,  dissolved  in  hot  alcohol,  a  little  water 
added  so  that  a  slight  opalescence  takes  place,  and  the 
whole  allowed  to  cool.  The  cholalic  acid  forms  in 
tetraedral  crystals, f  or,  according  to  Strecker,  rarely  in 
quadrate-octaedra.  They  are  colourless,  shining,  easily 
broken.  They  have  a  somewhat  bitter  taste,  with  a 
scarcely  noticeable  sweet  after-taste.  J  They  need  750 
parts  of  boiling,  and  4000  of  cold,  water  for  solution. 
They  are  readily  soluble  in  boiling  alcohol,  but  on 
cooling  separate  out.  1000  parts  of  cold  alcohol  of  70 
per  cent,  keep  48  parts  dissolved.  Hoppe-Seyler  says 
the  crystals  are  hardly  soluble  in  sether  ;  Strecker  that 
one  is  soluble  in  27  parts  of  sether. 

The  amorphous  variety,  according  to  Hoppe-Seyler, 
is  like  wax  and  may  be  kneaded.  It  is  somewhat 
soluble  in  water,  somewhat  more  in  sether,  and  very 
soluble  in  alcohol. 

The  formula  for  cholalic  acid  is  C^'^H'^°0^  Its  rational 
formula  is  unknown.  The  crystals  from  sether  contain 
2  molecules  of  water,  those  from  alcohol  5. 

Cholalic  acid  combines  readily  with  alkalies  and  drives 
out  carbonic  acid  from  its  combination  with  them.  The 
alkaline   salts   are  all  soluble  in  water :    the  baryta  and 


•  Strecker,  Annalcn  d.  Chetnle  unci  Pharm.  1848,  Bd.  Ixvii.  p.  3. 
f  Hoppe-Seyler,  Handb.  d.  phys.  u.  path.  chcm.  Analyse.  Berlin,  1865,  p.  90. 
J  Trifanovsky,  {Arch.  f.  d.  g.  Phys.  1874,  Bd.  ix.  p.  495)  says  cholalic  acid  has 
an  intensely  bitter  taste  without  any  sweet  after  taste. 


Dy  sly  sin  and  Choloidic  Acid.  23 

lime-salts  are  with  trouble  soluble  in  cold  water,  but 
more  easily  in  hot,  are  very  soluble  in  alcohol.  They 
form  fine  needles,  often  stellate.  The  cholalates  of  lead 
and  silver  are  insoluble  in  water,  but  soluble  in  hot 
alcohol. 

Cholalic  acid  gives  Pettenkofer's  reaction  ;  it  has  a 
dextro-rotatory  action  on  polarised  light :  -f-24°'55  for 
red,  and  4-27°'66  for  yellow,  light.*  It  dissolves  the 
red  blood  corpuscles. f 

Dy  sly  sin,  a  body  noted  and  named  by  Berzelius,J  is 
formed  by  heating  cholalic  acid  to  igo°  or  200°  C  when 
the  acid  is  split  up  into  dyslysin  and  water : 

Cholalic  acid.  Dyslysin. 

(324^4005  _  2   (H^O)  =  O'WO^ 

By  boiling  with  potash,  dyslysin  takes  up  water  and 
becomes  again  cholalic  acid.  The  same  decomposition 
takes  place  on  boiling  cholalic  acid  with  acids.  A 
mucilaginous  body  of  a  brown  colour  is  separated. 
This  is  insoluble  in  water  and  cold  alcohol ;  slightly 
soluble  in  hot  alcohol,  soluble  in  aether.  It  is  not  taken 
up  by  ammonia  or  potash  ;  by  boiling  with  alcoholic 
potash  or  fusing  with  potash  it  is  dissolved,  and  on 
adding  acids  a  body  is  thrown  down  which  is  no  longer 
dyslysin  but  choloidic  acid. 

Choloidic  acid,  a.  body  first  named  by  Demar9ay,§ 
has  been  further  investigated  by  Strecker.||  At  ordin- 
ary temperatures  it  is  firm  and  white,  often,  however, 
somewhat  coloured.  It  fuses  in  boiling  water  without 
being  dissolved.      When   dry  it  fuses  at  over   150°  C. 


*  HoippeSeyler,  Arch.  f.  path.  Anat.  1858,  Bd.  xv.  p.  138. 

f  Idem,  ibid.  1862,  Bd.  xxv.  p.  183.  Baumstark  has  published  some  interesting 
observations  on  cholalic  acid.  (Berichte  d.  deutschen  chem.  Gesellschaft  zu  Berlin, 
iSj^,  Bd.  vi.  p.  1185.) 

X  Berzelius,  (Annalen  d.  Cheinie  u.  Pharm.  1840,  Bd.  xxxiii.  p.  147),  calls  it  thus 
from  its  difficult  solubility:  ^u;  and  Xviris. 

§  Demargay,  Annates  de  chimie  et  de  physique,  1838,  t.  Ixvii.  p.  ig8. 

II  Strecker,  Annalen  d.  Chemie  und  Pharm,  1848,  Bd.  Ixvii.  p.  22. 


24  Cholonic  Acid. 

The  alcoholic  solution  is  made  opalescent  by  water  and 
is  acid  to  litmus.  In  aether  it  is  onl}^  slightly  soluble. 
It  is  best  purified  by  solution  in  alcohol  and  precipitation 
by  aether.  It  combines  with  bases  and  drives  out  car- 
bonic acid  by  the  aid  of  heat.  The  salts  of  choloidic 
acid  are  soluble  in  water  and  alcohol,  but  insoluble  in 
aether. 

The  weakCvSt  acids  drive  out  choloidic  acid,  even  a 
stream  of  carbonic  acid.  The  taste  is  purely  bitter, 
without  any  sweet  after-taste.  The  formula  which 
Strecker  gives  is  C^^H^^O^,  on  the  old  system. 

Hoppe-Seyler,  however,  doubts  if  this  choloidic  acid 
be  anything  but  cholalic*  The  body  which  Strecker 
analysed  was  probably  only  a  mixture  of  cholalic  acid, 
dyslysin,  and  cholonic  acid.  Like  cholalic  acid,  the 
body  obtained  by  Strecker's  process  crystallises  in  oc- 
taedra  and  tetraedra  ;  and  the  crystals  by  drying  lose 
io'2.per  cent,  of  water.  The  formula,  after  Gerhardt, 
is  C^^H^°02  +  2\  H'O,  which  equals  9-93  per  cent,  of 
water.  It  has  much  the  same  action  on  polarised  light 
as  cholalic  acid. 

Cholalic  acid  in  alcoholic  solution  =  -f  3S°'2. 

Acid  prepared  from  dyslysin  ,,  ,,        =  +  3S'4- 

Cholalate  of  potash  ,,  „        =  4-  3i'4. 

Salt  of  potash  from  dyslysin  ,,  ,,=-]-  30"8. 

The  baryta  salt  is  insoluble  in  water  and  thus  is  dis- 
tinguished from  glycocholic  and  cholalic  acid.  Baum- 
stark,  on  the  other  hand,  believes  that  a  distinct  cho- 
loidic acid  does  exist. j* 

Cholonic  acid  is  a  nitrogenous  derivative  from  glyco- 
cholic acid.  If  glycocholic  acid  be  added  to  strong 
sulphuric  acid,  the  glycocholic  acid  is  dissolved  ;  but  if 
the  mixture  be  warmed,  cholonic  acid  separates,  as  an 

*  Hoppe-Seyler,  Jonrna]  f.  pract.  Cliemic,  1863,  Bd.  Ixxxix.  p.  83. 

f  Baumstark,  Berichte  dcr  dcntschen  chetti.  Gcscllschaft  zu  Berlin.,  1873,  Bd.  vi. 

r-  1187- 


Cholonic  Acid.  25 

amorphous  precipitate,  which  is  not  soluble  in  water  but 
is  soluble  in  alcohol.  It  is  not  crystallisable.  This  acid 
is  also  formed  with  cholalic  acid  when  glycocholic  acid  is 
boiled  with  hydrochloric  acid.  Its  formula  isC^^H'^'NO^ 
The  dextro-rotatory  action  of  cholonic  acid  is  the  same 
as  that  of  glycocholic  acid. 

Parke  did  not  succeed  in  getting  from  taurocholic 
acid  an  acid  analogous  to  the  cholonic  acid  derived 
from  glycocholic  acid.* 

*  J.  Parke,  Hoppe-Seyler's  Med.  Chem.  Unterstcchungen,  Berlin,  1866,  p.  161. 


CHAPTER    II. 

The  Bile  Pigments. 

The  biliary  pigments  seem  to  have  been  first  studied 
by  the  Illustrious  Berzelius,*  afterwards  by  Scherer,']' 
Hein,{  and  Helntz.§  Stadeler  and  Maly  have  paid 
special  attention  to  these  colouring  matters. 

The  name  cholepyrrhin  Is  commonly  said  to  have 
been  given  by  Berzelius  to  the  orange  red  pigment  of 
the  bile.  F.  Simon  invented  a  barbarous  word,  bili- 
phaelnjl  compounded  of  Greek  and  Latin,  the  use  of 
which  has  been  unfortunately  endorsed  by  Heintz. 
Dr.  Thudichum  uses  the  word  cholophaeln,^  to  avoid 
this  bastard  word.  Stadeler  called  this  pigment  bili- 
rubin, forming  the  word  with  a  cognomen  like  the  other 
names  which  Berzelius  used ;  biliverdin,  bllifulvin, 
and  the  like.**  Maly  has  continued  the  use  of  the  name 
cholepyrrhin. ff  The  name  bilirubin  is  so  convenient 
and  so  commonly  used  that  I  shall  adopt  It  in  the 
following  pages. 

The  colouring  matters  of  the  bile  do  not  seem  to  give 
any  absorption  bands  In  the  spectrum;  as  Thudichum, J:J 

*  Berzelius,  Annalen  d.  Cheniie  u.  Pharni,  1840,  Bd.  xxxiii.  p.  139. 

f  Scherer,  ibid.  1845,  Bd.  liii.  p.  377. 

%  Hein,  Journal  f.  pr act.  Chemie,  1847,  ^^-  ^^-  P-  47- 

§  Heintz,  Poggendorff's  Annalen  d,  Physik  u.  Chcntie,  1851,  bd.  Ixxxiv.  p.  106. 

II  Simon,  (Animal  Chemistry,  1845,  Sydenham  Soc.  Edition  vol.  i.  p.  43,)  says 
that  cholepyrrhin  was  first  used  by  Berzelius,  and  biliphaein  by  Simon. 

%  Thudichum,  Tenth  Report  of  the  Medical  Officer  of  the  Privy  Council,  London, 
1868,  p.  243. 

**  Stadeler,  Annalen  d.  Chemie  u.  Pharm.  1864,  Bd.  cxxxii.  p.  323. 

ff  Maly's  observations  will  be  found  in  the  publications  named  below:  Sitzungs- 
berichte  d.  math.-naturw.  Classe  d.  k.  Akademie  der  Wissenschaften,  Wien  1868, 
Bd.  Ivii.  Abth.  ii.  p.  97.  Ibid.  1869,  Bd-  lix.  Abth.  ii.  p.  597.  Ibid.  Jahrg.  1874, 
Bd.  Ixx.  Abth.  iii.  p.  72:  also  in  Annalen  der  Chemie  und  Pharmacie,  1872,  Bd. 
clxiii.  p.  77.  Ibid.  1876,  Bd.  clxxxi.  p.  106. 

XX  Thudichum,  op.  cit.  p.  251. 


Bilirubin.  27 

Preyer,*  and  Vierordtf  agree.  It  is  only  when  they  are 
subjected  to  oxydising  agents  that  these  bands  make 
their  appearance.  Maly  noted  that  a  solution  of  biliru- 
bin in  chloroform  removed  the  blue  and  violet  out  of 
the  spectrum  up  to  70 ;  and  that  even  very  dilute 
solutions  removed  the  violet  end  of  the  spectrum. 
Biliverdin  in  alcoholic  solution  removed  both  ends  of 
the  spectrum.  J  Dr.  Dalton  has  described§  an  extreme 
shortness  of  the  bile  spectrum  with  a  band,  which  he 
thinks  characteristic,  at  C.  This  band  is  best  seen  in 
bile  which  has  a  distinct  green  colour ;  it  is  not  so  well 
seen  if  the  bile  be  brown  or  yellow ;  if  bile  lose  its 
green  colour,  the  band  disappears,  but  is  restored  if  the 
green  colour  be  brought  back  by  adding  iodine.  Dr. 
Dalton  thinks  this  band  to  be  due  probably  to  the 
presence  of  biliverdin.  Another  band  or  two  may 
sometimes  be  seen  at  D  or  D  30  E,  but  never  so 
distinctly  as  the  band  at  C. 

Cholepyrrhin,  bilifulvin,  or  bilirubin,  has  not  been 
studied  much  as  a  product  direct  from  the  bile,  but  as  a 
constituent  of  gall  stones  from  men  or  oxen  in  which  it  ap- 
pears in  combination  with  calcium.  Maly  recommends 
the  gall  vStones  to  be  broken  up,  boiled  with  alcohol  and 
filtered  hot.  The  brown  residue  on  the  filter  is  washed 
with  aether  and  digested  with  acetic  acid.  The  acid 
solution  is  filtered,  and  the  residue  washed  with  water 
and  alcohol.  The  remaining  powder  is  now  dried  and 
digested  for  several  days  in  chloroform  at  the  ordinary 
temperature,  or  for  a  few  hours  in  a  water  bath.  The 
chloroform  takes  up  the  pigment,  and  the  bilirubin  is 
obtained  by  distilling  off  the  chloroform,  and  washing 


•  Preyer,  Die  Blutkrystalle,  Jena  1871,  p.  187. 
f  Vierordt,  Zeitschriftf.  Biologie,  1874,  Bd.  x.  pp.  44  and  48. 
X  Maly,  Sitzungsberichte  d.  math.-naturw,  Classe  d.  k.Akad.  der  Wissenschaften, 
Wien,  1868,  Bd.  Ivii.  Abth.  ii.  p.  106. 

§  Dalton,  New  York  Med.  jfournal,  1874,  vol.  xix.  p.  579. 


28  Stddeler  and  Thudichuiri's  Process. 

with  spirit.     If  the  pigment  be  wished  for  very  pure,  the 
whole  process  had  better  be  repeated  once  or  twice.* 

Stadeler  recommends  another  process.  The  gall 
stones  are  digested  in  aether,  and  the  residue  extracted 
with  hot  water,  dried,  and  then  treated  with  chloroform. 
This  gives  an  impure  solution  of  bilirubin.  It  must  be 
evaporated  to  dryness  and  then  treated  with  hydro- 
chloric acid.  Carbonic  acid  is  given  off,  and  the  violet 
filtrate  contains  a  great  quantity  of  lime  and  magnesia. 
The  residue  on  the  filter  must  be  washed  and  dried, 
and  is  then  of  a  dark  brown  green.  To  purify  it,  the 
bilirubin  must  be  dissolved  several  times  in  chloroform, 
the  filtrate  evaporated,  and  the  residue  washed  with 
sether  and  spirit.  The  washings  with  alcohol  are  always 
more  or  less  green,  while  the  bilirubin  remains  on  the 
filter  as  an  orange-red  granular-crystalline  powder. 

Dr.  Thudichum  recommends  a  long  and  troublesome 
process.  Gall  stones  from  the  ox  are  powdered  and 
made  into  a  dough  with  a  little  hot  water ;  an  excess  of 
hot  water  added  and  the  whole  well  stirred.  After  stand- 
ing for  several  days  the  fluid  is  separated  by  decantation, 
a  process  frequently  repeated.  At  last  the  whole  is 
thrown  upon  a  filter,  and  the  paste  left  is  put  into  a 
flask  with  a  large  quantity  of  spirit  and  boiled.  After 
exhausting  the  powder  with  alcohol,  it  is  treated  for 
several  days  with  cold  dilute  hydrochloric  acid.  The 
powder  is  washed  by  decantation,  lastly  On  the  filter,  and 
a  second  time  with  alcohol.  After  this  the  powder  may  be 
washed  with  aether,  but  if  the  foregoing  operations  have 
been  properly  performed,  this  last  process  will  be  un- 
necessary. When  dried,  the  powder  is  boiled  with  pure 
chloroform,  and  exhausted  with  this  liquid.  The  filtered 
solution  is  evaporated,  and  the  residue  with  absolute 
alcohol  till  the  latter  be  nearly  colourless,  and  the  resi- 
due on  the  filter  red  without  any  admixture  of  green. f 

*  Maly,  op.  cit.  p.  96.  f  Thudichum,  op.  cit.  p.  241. 


Bilirubin.  29 

Heintz  appears  to  be  the  first  who  gave  a  distinct 
formula  for  bilirubin.*  Scherer  and  Hein  made  ele- 
mentary analyses,  but  did  not  succeed  in  composing  a 
distinct  formula.  According  to  Heintz  the  formula  is 
D^H'^N'O^.  Stadeler  and  Maly,  however,  both  give 
D^H^'N^O'^  or  in  the  new  notation  C^'H^^N^O^,  and  this 
appears  to  be  generally  accepted.  Maly  believes  that 
bilirubin  is  the  amide  of  biliverdin  which  possesses  the 
properties  of  an  acid  in  uniting  with  bases. f  Dr. 
Thudichum,  however,  denies  this,  and  asserts  the  for- 
mula to  be  C9H9NO^t 

Dr.  Thudichum  describes  two  modifications  of  the  red 
colouring  matter  of  the  bile  ;  the  one,  amorphous,  of  a 
bright  red  colour,  which  he  calls  bilirubin  ;  the  other, 
crystalline,  of  a  purple-brown  colour,  which  he  calls 
biliphsein  or  cholophsein.  He  regards  them  as  identical 
chemical  substances.  The  crystals  belonged  to  the 
rhombic  system,  "being  prisms  in  some  crystalliza- 
tions, simple,  and  with  nearly  obtuse  right  angles,  in 
others  with  sharp  angles  on  the  one,  obtuse  angles  on 
the  next  edge,  and  planes  from  secondary  prisms  cut- 
ting off  the  sharp  angles  of  the  primary  ones." 

Bilirubin  heated  on  platinum  foil  leaves  no  residue 
behind. 

Stadeler  says  that  amorphous  bilirubin  is  orange 
coloured  ;  the  crystals  show  the  dark  red  of  chromic 
acid.  He  finds  that  good  crystals  can  rarely  be  got  from 
the  solution  in  chloroform  ;  better  are  had  direct  from 
the  bile.  Maly  describes  them  as  doubly  convex,  like 
the  section  of  a  biconvex  lens. 

In  water,  bilirubin  appears  to  be  quite  insoluble, 
slightly  in  aether,  and  a  little  more  in  spirit.  The  alco- 
holic solution  made  while  hot    is  golden  yellow,  when 

*  Heintz,  op.  cit.  p.  114. 

\  Maly,  Ccntralblatt  f.  d.  med.  Wiss.  1864,  p.  640. 

\  Thudichum,  op.  cit.  pp.  241  and  244. 


30  Bilirubin. 

cold  it  becomes  brighter,  and  if  filtered  the  greater  part 
of  the  pigment  adheres  to  the  paper  so  that  the  filtrate 
shows  only  a  slight  degree  of  yellowness.  Chloroform 
dissolves  bilirubin  even  in  the  cold  ;  the  more  crystal- 
line the  bilirubin,  the  slower  the  solution.  The  chloro- 
form acquires  a  yellow  or  pale  orange  colour.  A  sat- 
urated solution  is  dark  brown  red.  Sulphide  of  carbon  and 
benzol  are  also  good  solvents,  to  which  Dr.  Thudichum 
agrees,  but  Maly  says  that  this  last  only  dissolves 
inconsiderable  amounts.  This  last  observer  remarks 
that  bilirubin  is  insoluble  in  saliva  and  white  of  egg ; 
and  that  solution  of  soap  is  only  somewhat  coloured.  In 
hot  amylic  alcohol,  fatty  oils,  and  glycerine,  it  is  also  a 
little  soluble.  Stadeler  says  it  is  soluble  in  warm  tur- 
pentine and  fatty  oils. 

Bilirubin  is  soluble  in  ammonia  and  the  caustic  alka- 
lies, and  the  solutions  are  intensely  coloured.  Stadeler 
found  that  an  alkaline  solution  of  one  in  15000  was 
distinctly  orange  in  a  layer  15  millimeters  thick  ;  that 
is,  a  little  over  half  an  inch  ;  a  layer  of  the  same  thick- 
ness, of  one  in  20,000,  was  a  deep  golden  yellow ;  one 
in  25,000  to  100,000,  pure  yellow,  like  solutions  of 
chromate  of  potash.  A  yellow  colour  was  still  per- 
ceptible in  solutions  of  one  in  500,000 ;  and.  in  a  layer, 
two  inches  thick,  of  a  solution  of  one  in  a  miUion.  A  so- 
lution of  one  in  30,000  or  40,000  stained  the  skin  yellow. 
The  value  of  these  observations  will  be  seen  when  the 
amount  of  bilirubin  in  the  urine  of  jaundice  is  discussed, 
and  the  amount  of  bilirubin  which  is  secreted  by  the 
liver  in  obstruction  to  the  bile  ducts. 

The  alkaline  solution  is  thrown  down  by  acids. 
Strong  sulphuric  acid  dissolves  bilirubin  with  a  red 
brown  colour,  which  after  a  time  becomes  discoloured 
and  dirty  brown  green.  If  the  red  brown  solution  be 
poured  into  water,  dark  brown  flakes  are  thrown  down 
which  may  be   readily  filtered  from  the  colourless  solu- 


Derivatives  of  the  Bile  Pigments.  31 

tion.  Maly  says  that  the  body  remaining  on  the  filter 
is  no  longer  bilirubin  and  does  not  give  Gmelin's  re- 
action. This  is  denied  by  Stadeler,  who  notes  that  the 
red  in  the  play  of  colours  is  remarkably  fine. 

The  oxydising  action  of  nitric  acid  upon  bilirubin  has 
long  been  known  as  Gmelin's  test.  Stadeler  says  that 
a  quarter  of  a  milligramme  dissolved  in  4  C.C.  can  be 
readily  detected  by  this  means,  and  that  the  colours  still 
appear  in  a  solution  of  one  in  70,000  or  80,000.  The 
yellow  colour  is  changed  by  the  action  of  the  acid  into 
green,  then  blue,  violet,  ruby  red,  and  lastly  dirty 
yellow.  All  these  stages  of  oxydation  correspond  to 
bodies  which  can  be  isolated  and  preserved.  If  a  solu- 
tion of  bilirubin  in  chloroform  be  acted  on  by  a  drop 
or  two  of  nitric  acid,  and  spirit  added  as  soon  as  the 
blue  or  violet  colour  appears,  the  solution  becomes  deep 
blue  and  remains  so.  In  the  same  way  a  fine  green  or 
red  can  be  had,  according  to  the  time  at  which  the 
spirit  of  wine  is  added.  Heynsius  and  Campbell  have 
made  a  special  study  of  the  spectra  of  these  bodies.* 

The  derivatives  of  the  bile  pigments  cannot  be  more 
than  mentioned  here,  as  their  discussion  would  in  most 
points  be  foreign  to  the  object  of  this  work.  Their 
history  begins  with  Stadeler,  who  has  the  merit  of  being 
the  first  to  point  out  the  kindred  of  the  blue  product  of 
the  oxydation  of  bilirubin  with  the  indigo  colouring 
matter  of  the  urine. f  In  1869  Jaffe  named  the  colour- 
ing matter  of  the  urine  urobilin,  because  he  believed  it  to 
be  a  derivative  of  the  bile  pigment,  whether  by  oxydation 
or  not  was  left  undetermined.  J  Heynsius  and  Campbell 
believe  it  to  be  due  to  oxydation  ;§  Maly,  however,  to  re- 

*  Heynsius  and  Campbell,  Arch.f.d.  ges.  Phys.  1871,  Bd.  iv.  p.  497. 

f  Stadeler,  op.  cit.  p.  333. 

X  Jaffe,  Arch.f.  path.  Anat.  1869,  Bd.  xlvii.  p.  423.     See  also  Arch.f.  ges.  Phys. 
1868,  Bd.  i.  p.  262.   Magendie  (Precis  elan,  de  Phys.  Paris,  1836,  4e  ed.  t.  ii.  p.  474, 
notej  conjectures  :  II  est  probable  que  la  matiere  jaune  de  la  bile  est  aussi  celle  qui 
colore  le  serum  du  sang,  I'urine  etc. 
■    §  Heynsius  and  Campbell,  loc.  cit. 


32  HcEmatoidin  and  Bilirubin. 

duction.*  Vanlair  and  Masius  describe  another  deriva- 
tive, found  in  abundance  in  the  faeces,  which  is  closely 
allied  to  urobilin,  and  which  they  name  sterco-bilin.f 

The  relation  of  the  bile  pigments  to  the  colouring 
matters  of  the  blood  is  that  which  has  the  greatest 
attraction  for  the  physician,  inasmuch  as  much  of  the 
doctrine  of  haematagenous  jaundice  depends  upon  the 
belief  that  the  two  bodies  are  the  same.  Doubtless  the 
idea  that  haematoidin  and  bilirubin  are  identical  has 
much  to  recommend  it  to  the  notice  of  physiological 
chemists,  but  the  notion  has,  I  think,  been  asserted 
with  scarcely  sufficient  proof.  It  is,  however,  an  exam- 
ple of  the  rashness  which  characterises  the  present 
generation  of  physiological  chemists ;  they  make  up 
for  the  extreme  uncertainty  of  their  opinions  by  an 
increased  boldness  of  assertion. 

Saunders,  more  than  80  years  ago,  thought  that  there 
might  be  some  relation  between  the  colouring  matters 
of  the  blood  and  the  bile  pigments.  J  Frerichs,  in  his 
essay  on  the  chemistry  of  human  bile,  makes  the  short 
remark  that  the  colouring  matters  are  allied  on  one  side 
to  haematin  and  on  the  other  to  black  pigment  ;§  but 
two  years  later  Virchow,  in  the  midst  of  his  well-known 
work  on  the  pathological  pigments,  opened  the  question 
of  the  relation  of  the  bile  colouring  matter  to  the  blood. 
Speaking  of  the  red  sealing-wax  like  matter  which  is  so 

*  Maly,  Annal.  d.  Chemie.  ii.  Phavm.  1872,  Bd.  clxiii.  p.  77.  He  has  named  the 
last  product  of  oxydation  choletelin,  from  riXos,  end.  Sitzungsbb.  d.math.-naturw. 
Classe  d.  k.  Akad.  d.  Wiss.  Wien,  1869.  Bd.  lix.  Abth.  ii.  p.  605. 

f  Vanlair  and  Masius,  Ccntralblntt  f.  d.  med.  Wiss.  1871,  p.  369.  See  also 
Stokvis,  ibid.  1872,  pp.  3  and  785,  and  1873,  p.  211 ;  and  Journal  of  the  Chemical 
Society,  1872,  vol.  xxv.  p.  308,  and  1873,  vol.  xxvi.  pp.  78  and  288.  Vierordt, 
Zeitschriftf.  Biologic,  1873.  Bd.  ix.  p.  160,  and  1874,  Bd.  x.  p.  21. 

\  Saunders,  A  Treatise  on  the  Structure,  Economy,  and  Diseases  of  the  Liver, 
London,  1803,  third  edit.  p.  147.  "  Green  and  bitter  bile  being  in  common  to  all 
animals  with  red  blood,  and  found  only  in  such,  makes  it  probable  that  there  is 
some  relative  connexion  between  this  fluid  and  the  colouring  matter  of  the  blood, 
by  the  red  particles  contributing  more  especially  to  its  formation."     Cf.  p.  160. 

§  Frerichs,  Hannoversche  Annalen,  1845,  Jahrg.  v.  p.  145. 


HcBmatoidin  and  Bilirubin.  33 

often  found  in  echinococci  cysts  in  the  liver,  he  says  that, 
in  cases  where  this  matter  had  undoubtedly  had  its  origin 
in  bile,  he  had  found  the  crystals  on  the  wall  of  the  cyst 
very  like  those  of  old  blood  clots.  Some  of  these  crystals 
he  attempted  to  examine  chemically  ;  but  naturally  the 
tests  could  not  be  very  satisfactorily  applied  with  so 
small  a  quantity,  and  with  such  impure  materials.  He 
found  the  crystals  insoluble  in  aether,  alcohol,  or  alcohol 
containing  sulphuric  acid,  or  turpentine.  No  change 
took  place  with  chlorine  vapour,  while  old  corpora  lutea 
were  completely  bleached.  Both  were  acted  on  by  sul- 
phide of  ammonium,  the  crystals  remaining  unchanged, 
while  the  corpora  lutea  became  black.  With  nitric  acid 
they  quickly  became  brown-red,  then  intensely  green, 
blue,  and  rose  coloured.  The  crystals  were  soluble  in 
alkalies.  Virchow  thinks  these  observations  make  it  very 
probable  that  blood  colouring  matter  may  be  changed 
into  bile  pigment.* 

Robin  also  gave  great  help  to  Virchow's  notions.  A 
mass,  weighing  3  grammes,  of  the  red  colouring  mat- 
ter taken  from  hydatid  cysts  of  the  liver,  was  found  to 
consist  entirely  of  very  regular  crystals,  quite  like 
those  described  by  Virchow.  They  were  completely 
dissipated  by  heat  and  were  insoluble  in  water,  alcohol, 
aether,  glycerine,  and  acetic  acid  ;  but  soluble  in  am- 
monia ;  nitric  acid  quickly  dissolved  the  crystals  with 
effervescence,  leaving  a  red  solution  ;  sulphuric  acid  did 
not  dissolve  them,  but  they  became  greenish.  Robin 
thought  the  mass  had  its  source  in  extravasated  blood. 
An  elementary  analysis  gave  the  following  results  : 


10-5050. 


*  Virchow,  Arcli.f.  path,  Anat.  1S47,  ^^-  ••  P-  ^-7- 

D 


Carbon 

65  -046. 

65-851. 

Hydrogen 

6-37- 

6-465. 

Nitrogen 

Oxygen 

i8-o888. 

17-1788. 

Ashes 

00-0002. 

00-0002. 

34  Hcematoidin  and  Bilirubin. 

Stadeler  and   Maly  give  as  the  percentage   of  their 
analyses  of  bilirubin,  the  following  figures  : 


Stadeler.* 

Maly.+ 

Carbon 

67-iS- 

67- 16. 

Hydrogen 

6-.27 

6-20. 

Nitrogen 

9-59. 

Oxygen 

16-99. 

The  percentage  analyses  of  these  two  bodies,  there- 
fore, correspond  in  many  particulars.  Robin  compares 
his  analysis  with  one  of  Mulder's,  of  hasmatosin,  and 
appears  to  think  that  the  substance  analysed  was  a 
derivative  of  the  blood,  without  the  iron  salts.  He  re- 
marks that  the  amount  of  blood  extravasated  in  this 
cyst  must  have  equalled  1800  grammes  at  least  in  order 
to  furnish  this  quantity,  3  grammes  of  colouring  matter.  J 
It  is  hard  to  see  how  so  much  blood  can  have  been  poured 
into  the  cyst,  but  it  is  easy  to  understand  that  a  great 
deal  of  bile  might  have  found  its  way  into  the  sac  ;  it  is 
common  to  find  this  red  sealing-wax  like  stuff  in  cysts 
communicating  with  the  bile  ducts;  Virchow's  opinion§ 
that  this  red  matter  had  its  source  in  the  bile  would  seem 
to  be  correct.  It  is  very  likely  that  Robin  analysed  only 
an  impure  bilirubin.  Stadeler  points  out  that  Robin's 
formula,  C'^H^NO^  is  not  justified  by  the  analysis,  but 
that  C3°H'^N^0^  would  be  more  correct ;  the  hydrogen 
only  in  this  case  being  'i  and  '2  per  cent,  less  than 
found.  II 

Zenker  and  Funke  say  that  bilifulvin,  that  is,  bilirubin, 
either  spontaneously  or  by  treatment  with  aether,  changes 
into  fine  large  crystals  which  shew  "all  the  properties" 


*  Stadeler,  Amialcn  d.  Chcmic  u.Pharmacic,  1864,  Bd.  cxxxii.  p.  328. 
f  Maly,  Sitzungsbcrichte  dcr  math.   wiss.   Classe  der  k.  Akad.  Wien,  1868,  Bd. 
Ivii.  Abth.  ii.  p.  gy. 

X  Robin,  Comptcs  rcndus,  1855,  t.  xli.  p.  506. 

§  Virchow,  loc.  cit. 

II  Stadeler,  op.  cit.  p.  348. 


Hcematoidin  and  Bilirubin.  35 

of  hsematoidin,  and  are  therefore  identical  with  it.*  It 
would  be,  however,  interesting  to  know  what  "all  the 
properties"  of  hasmatoidin  are. 

Jaffe  examined  an  old  haemorrhage  into  the  brain  with 
a  view  to  getting  bilifulvin  from  it.  It  was  dried  in  a 
water  bath,  cut  up  fine,  and  extracted  with  chloroform, 
after  being  first  moistened  with  a  little  alcohol.  The 
extract  becoming  of  a  deep  yellow  colour  :  the  chloro- 
form was  then  distilled  until  but  a  few  drops  were  left, 
and  these  were  allowed  to  evaporate  spontaneously  in  a 
watch-glass.  This  should  be  carried  on  in  the  dark,  in 
order  to  hinder  oxydation.  The  crystals  left  after  this 
evaporation  were  golden  yellow  in  colour,  and  remark- 
ably fine  ;  they  corresponded  closely  in  shape  to  those  of 
hsematoidin.  Jaffe,  wishing  to  free  them  from  fat,  found 
a  good  number  of  them  soluble  in  aether.  The  re- 
mainder was  easily  soluble  in  carbonate  of  soda.  The 
yellow  solution  became  green  during  filtration.  A  small 
residue  was  lastly  treated  under  the  microscope  with 
nitric  acid.  The  crystals  shewed  the  well-known  re- 
action of  bile  pigment,  becoming  first  green,  then  blue. 
Jaffe  had  no  longer  any  doubt  that  by  simple  recrystal- 
lization  of  hsematoidin,  bilifulvin  can  be  had  :  therefore 
that  the  two  bodies  are  identical.  It  must  be,  however, 
noted,  that  Jaffe  confesses  that  he  was  unable  to  obtain 
bilifulvin  from  other  old  haemorrhages  which  had  lain 
long  in  spirit. t 

Hoppe-Seyler  found  in  the  fluid  from  a  cyst  in  the 
breast,  crystals,  which  from  their  crystallisation  and  re-- 
action  with  nitric  acid  he  judged  to  be  the  same  as  bile 
pigment,' and  yet  from  the  source,  as  in  Jaffe's,  could  not 
have  had  their  origin  in  the  bile.  J 

Valentiner  is  said  to  have  made    some  observations 

*  Funke,  Lekrbicch  d.  Physiologie,  Leipzig,  i860,  3te  Aufl.  Bd.  i.  p.  246. 
f  Jaffe,  Archiv  f.  path.  Anat.  1862.  Bd.  xxiii.  p.  192. 
X  Hoppe-Seyler,  ibid.  1862,  Bd.  xxiv.  p.  10. 

D2 


35  HcBinatoidin  and  Bilirubin. 

which  favoured  the  behef  that  haematoidin  and  biliru- 
bin are  identical,  finding  crystals  of  the  same  shape  as 
haematoidin  in  an  extract  of  bile  with  chloroform.  I 
have  not,  however,  been  able  to  see  the  journal*  in 
which  the  paper  was  published,  so  that  I  can  give  no 
trustworthy  account  of  its  contents. 

Stadeler,  criticising  Valentiner's  work,  says  that  he  has 
always  found  the  crystals  of  bilirubin  to  be  less  perfect, 
as  the  solution  out  of  which  they  form  approaches 
purity.  If  bile  be  shaken  up  with  chloroform,  as  in 
Valentiner's  work,  and  the  chloroform  allowed  to  evap- 
orate, there  form  orange  coloured  elliptic  tables,  or  very 
small,  almost  right  angled,  tables,  the  angles  of  which 
are  very  different  from  those  of  haematoidin. 

The  results  were  the  same  in  nearly  every  case,  the 
rhomboid  forms  were  always  recognised,  with  some 
slight  changes  in  the  sides  and  angles  in  which  the 
diagonals  of  the  rhomboids  were  marked  by  changes 
of  colour.  Only  as  an  exception  were  seen  forms 
which  approached  the  ordinary  haematoidin  appearance. 
Stadeler  also  found  that  the  crystals  which  formed 
out  of  benzol  and  sulphide  of  carbon  solutions  showed 
greater  resemblance  to  haematoidin ;  haematoidin  has 
never  convex  surfaces,  while  these  are  commonly  seen 
in  bilirubin  crystals,  so  that  at  first  sight  they  may  be 
mistaken  for  uric  acid.f 

The  important  point,  however,  is  the  analysis,  and 
it  would  seem  that  an  analysis  of  haematoidin  has 
yet  to  be  made.  Holm,  under  Stadeler's  guidance, 
and  in  his  laboratory  at  Zurich,  has  attempted 
a  further  study  of  the  differences  between  haema- 
toidin and  bilirubin. f  He  first  tried  to  win  from 
old   haemorrhages   in  the   brain  a  sufficient  amount  of 

•  Valentiner,  Giinsburg's  Zcitschrift  f.  kliii.  Med.  1858,  p.  46. 
f  Stadeler,  op.  cit.  p.  344. 

*  Holm,  youriujl  fur  prakthchc  Clicniic,  1867,  Bd.  c.  p.  142. 


HcBinatoidin  and  Bilirubin.  37 

haematoidin  by  means  of  extraction  with  chloroform. 
He  found,  however,  that  but  very  Httle  could  be  had  in 
this  way.  He  noted,  however,  as  Salkowski  has  done, 
that  the  yellow  colour  of  the  chloroform  extract  changed 
by  exposure  to  the  light  into  a  bright  green.  The  next 
attempt  was  on  the  corpora  liitea  of  cows,  in  these  good 
crystals  were  rarely  met  with.  The  haematoidin  was 
extracted  by  chloroform  or  sulphide  of  carbon,  from 
which  it  could  readily  be  obtained  in  crystals.  The 
crystals  were  found  to  be  acute  angled  triangular  tables, 
of  which  one  side  is  convex  ;  this  convex  side  can  be 
replaced  by  two  straight  lines  whereby  the  tables  be- 
come somewhat  of  the  shape  of  a  delta.  Two  of  these 
triangular  tables  may  be  joined  so  as  to  present  the 
appearance  of  the  ordinary  rhombic  crystals  of  haema- 
toidin. 

It  has  been  said  that  haematoidin  is  soluble  in  aether 
and  sulphide  of  carbon.  In  absolute  aether  it  is  less 
soluble  than  in  these.  It  is  not  soluble  in  absolute 
alcohol  or  water,  nor  in  ammonia  or  soda.  Acetic  acid 
(glacial)  dissolves  it  when  warmed,  and  if  to  this  solu- 
tion a  drop  of  ordinary  nitric  acid  be  added,  the  mixture 
becomes  blue,  but  this  colour  immediately  disappears, 
and  the  solution  remains  colourless.  The  solution  of 
haematoidin  in  chloroform  gives  no  Gmelin's  reaction 
with  nitric  acid,  nor  even  the  blue  colour  just  spoken 
of:  the  colour  of  the  yellow  solution  is  simply  discharged. 

Holm  sums  up  :  Bilirubin  and  haematoidin  have  not 
only  different  forms  and  colours  but  different  chemical 
properties.  The  former  shows  the  properties  of  a 
weak  acid  ;  the  latter  is  indifferent. 

Bilirubin  is  soluble  in  sulphide  of  carbon  with  a 
golden  yellow  colour ;  haematoidin  with  brilliant  red. 

Bilirubin  is  insoluble  in  aether  ;  haematoidin  soluble. 

Bilirubin  is  readily  soluble  in  alkalies ;  haematoidin 
insoluble. 


38  Hcematoidin  and  Bilirubin. 

Salkowski,  however,  suffers  not  this  statement 
of  Holm's  to  go  undenied.  The  contents  of  a 
thyroid  cyst  were  obtained  by  puncture  during  hfe. 
The  mass  showed  all  the  appearances  of  bilirubin. 
Under  the  microscope  good  rhombic  tables  were  seen 
which  were  readily  soluble  in  chloroform  with  golden 
yellow  colour,  and  a  little  also  in  aether.  Both  these 
solutions  readily  gave  up  this  body  when  shaken  with  a 
weak  soda  solution,  while  the  chloroform  or  aether  became 
colourless.  The  alkaline  solution  gave  the  well-known 
Gmelin's  reaction  with  nitric  acid,  and  not  merely  a 
rapidly  disappearing  blue,  as  Holm  found  with  his 
hsematoidin  solutions.  Exposed  to  the  air  the  solutions 
became  green. 

Salkowski  confesses,  however,  that  the  body  which 
he  extracted  was  so  small  in  amount  that  it  was  only 
enough  to  make  out  these  foregoing  properties.* 

Pre3'er,  so  well  known  for  his  researches  on  the 
blood  crystals,  is  very  strongly  of  opinion  that  biliru- 
bin and  hasmatoidin  are  not  identical.  He  finds  the 
spectrum  of  the  two  bodies  entirely  different.  The 
chloroform  extract  of  gall  stones  shows  in  the  most 
dilute,  as  well  as  in  the  most  saturated  solutions,  no 
absorption  bands  from  A  to  G.  With  increased  con- 
centration, the  refrangible  part  towards  the  green  gets 
more  and  more  dark  without  showing  bright  inter- 
vals. 

Now  the  haematoidin  extracted  by  chloroform  from  the 
corpus  luteiim  of  the  cow,  in  which  Preyer  noted  abun- 
dance of  haematoidin  crystals,  behaved  quite  differently. 
The  yellow  chloroform  extract  gave  a  characteristic 
spectrum ;  a  well-marked  absorption  band  between 
b  and  F,  close  to  F,  and  a  smaller  one  between  F  and 
G.      If   the  concentration  were  increased,   an  absorp- 

*  Salkowski,  McdicUiisch-Chcmischc  U liter suchungcn,  herausgeg.  von  Hoppe- 
Seyler,  Berlin,  1868.  Heft  iii.  p.  436. 


HcBinatoidin  and  Bilirubin. 


39 


tion   band  appeared  between    80    and    115,  while  red, 
orange,  yellow,  and  green  remained  bright. 

Preyer  found  the  same  spectrum  in  haematoldin 
crystals  from  an  old  haemorrhage  into  the  brain  ;  so 
that  it  is  not  another  body,  taken  up  from  the  corpus 
luteum  by  the  chloroform  which  gives  the  two  bands. 
Another  reason  that  bilirubin  is  different  from  haema- 
toldin is  the  great  colouring  power  of  the  former,  which 
the  latter  does  not  possess.  Also  in  aether  contain- 
ing fat,  haematoidin  is  soluble,  while  bilirubin  is  not, 
as  Preyer  has  convinced  himself.* 

Thudichum,  however,  asserts  that  the  body  which 
Holm,  Preyer,  and  other  observers  have  examined  is 
not  hffimatoidin  but  lutein  ;  and  that  lutein  differs 
altogether  from  bilirubin,  or  as  Thudichum  calls  it, 
cholophaein.f  The  lutein  of  Thudichum  appears  to 
resemble  the  luteo-h^matoidin  or  haemolutein  of 
Piccolo  and  Lieben.J 

In  conclusion,  it  may  be  observed  that  there  are  at 
present  scarcely  sufficient  data  for  the  formation  of  a 
trustworthy  opinion  that  bilirubin  and  haematoidin  are 
identical.  The  shape  of  the  crystals,  the  presence 
of  iron,  the  solubility  in  various  reagents,  are  given 
differently  by  different  observers. 

Kuhne§  and  Hoppe-Seyler||  boldly  cut  the  knot  by 
using  haematoidin  as  a  synonym  for  bilirubin  ;  but  if 
the  observations  of  Preyer  on  the  spectrum  of  the  two 
bodies  be  in  any  way  trustworthy,  it  will  hardly  be  pos- 
sible to  continue  this  assertion.  All  observers  who 
have  examined  the  spectrum  of  bilirubin  announce  it  to 
be  free  from  absorption  bands ;  but  even  the  hasmatin  free 

*  Preyer,  Die  Blutkrystalle,  Jena,  1871,  p.  188. 

f  Thudichum,  Proceedings  of  the  Royal  Society  of  London,  1869,  vol.  xvii.  p.  255. 
X  Piccolo   and   Lieben,   Giornale  di  scienze  naturali  ed  economiche,  Palermo, 
1866,  vol.  ii.  p.  258. 

§  Kiihne,  Lehrb.  d.  phys.  Chemie.  Leipzig,  1866,  p.  72. 

II  Hoppe-Seyler,  Handb,  d.  phys.  nnd  path,  chem,  analyse,  Berlin,  1865,  p.  161. 


40  Biliverdin. 

from  iron  shows  according  to  Hoppe-Seyler  four  absorp- 
tion bands  in  the  red,  yellow,  and  green.*  The  balance 
of  evidence  is  in  my  opinion  against  the  identity  of  the 
two  bodies. 

Bilirubin  enters  readily  into  combination  with  bases'}" 
and  these  combinations  for  the  most  part  are  insoluble 
in  water,  spirit,  aether,  or  chloroform.  The  best  known 
combination  is  that  with  calcium  so  often  met  with  in 
gall  stones.  It  may  be  prepared  by  decomposing  a 
weak  ammoniacal  solution  of  bilirubin  with  chloride  of 
calcium ;  the  bilirubin-calcium  is  thrown  down  as  a 
dark  red  precipitate.  Its  formula  according  to  Stadeler, 
who  wrote  in  the  prse-Gerhardtian  days,  is  C^^H'^CaN^O^: 
or  according  to  the  modern  notation  C'^H'^CaN^O^.  Ac- 
cording to  Maly,  bilirubin  is  the  amide  of  biliverdin 
which  possesses  the  properties  of  an  acid.  J 

Biliverdin.  The  name  biliverdin  was  first  used  by 
Berzelius  who  thought  this  green  pigment  of  the  bile  of 
herbivorous  animals  allied  to  the  vegetable  chlorophyll. § 
Heintzll  first  gave  it  a  formula  C'^H^NO^ ;  Maly,  how- 
ever, gives  a  formula  C"^H'**N'0^  which  differs  from  that 
above  in  containing  less  oxygen. 51  It  would  appear 
from  this  latter  that  biliverdin  is  only  bilirubin  with  one 
atom  of  oxygen  more,  as  is  seen  by  the  following  equa- 
tion, C'^H^^N^O^  +  0  =  C^^H'^N^O^  Stadeler  assumes 
that  bilirubin  takes  up  water  as  well  as  oxygen  in  be- 
coming biliverdin  and  adds  two   molecules  of  water  to 


*  Hoppe  Seyler,  Arch.  d.  path.  Anat.  1864,  Bd.  xxix.  p.  235. 

f  Thudichum  {Tenth  Report  Sec.  Lond.  1868,  p.  244),  gives  a  full  account  of  these. 

\  Maly,  Ccntralblattf.d.  med.  Wiss.  1864,  p.  640. 

§  Berzelius,  Annalen  d.  Chcmie,  1840,  Bd.  xxxiii.  pp.  140  and  177.  Biliverdin 
has  been  called  by  Dr.  Thudichum  cholochlorine  [Tenth  Report  of  the  Medical  Officer 
of  the  Privy  Council,  1868,  London,  p.  249.)  This  attempt  to  disturb  the  old  name 
is  to  be  regretted,  as  no  good  object  can  possibly  be  attained.  See  also  Thudi- 
chum, yournal  of  the  Chemical  Society,  1876,  vol.  ii.  p.  27. 

II  Heintz,  Poggendorft's  Annalen  d.  Physik  u.  Chcmie,  1857,  Bd.  Ixxxiv.  p.  117. 

IT  Maly,  op.  cit.  1868,  Bd.  Ivii.  Abth.  ii.  p.  105.  See  also  the  same  Sitzungs- 
berichte,  Jahrg.  1874,  Wien,  1875,  Bd.  Ixx.  Abth.  iii.  p.  72. 


Biliverdin. 


41 


the  formula :  but  this  theory  is  confessedly  founded 
upon  the  analysis  by  Heintz  of  an  impure  'biliverdin, 
so  that  in  this  matter  Maly's  formula  should  be  received 
rather  than  Stadeler's. 

Dr.  Thudichum  gives  the  formula  C^H^NO^  and  thinks 
that  biliverdin  arises  from  bilirubin  by  the  addition  of 
2  atoms  of  oxygen  and  subtraction  of  one  of  carbonic 
acid. 

Maly  says  that  there  are  three  sets  of  reagents  by 
means  of  which  bilirubin  can  be  converted  into  biliver- 
din :  acids,  alkalies,  and  bromine  and  iodine. 

Maly  finds  that  the  action  of  acetic  acid  and  chloro- 
form upon  bilirubin,  in  sealed  tubes,  and  aided  by  the 
heat  of  a  water  bath,  is  to  change  the  bilirubin,  into  a 
green  body.  The  change  of  colour  is  complete,  and  no 
other  reaction  shows  it  so  well.  Other  acids,  as  hydro- 
chloric, heated  with  bilirubin,  cause  the  formation  of  a 
green  body.  Phipson  has  recommended  the  use  of 
strong  sulphuric  acid  for  this  purpose.*  Maly  found 
that  anhydrous  sulphurous  acid  did  not  change  biliru- 
bin into  biliverdin,  when  heated  in  sealed  tubes  in  a 
water  bath:  the  alcoholic  solution  remained  pure  golden 
yellow.  This  seemed  to  show  that  the  oxygen  comes 
from  the  air,  not  from  the  acid,  as  in  presence  of  sul- 
phurous acid  there  could  scarcely  be  oxydation  of  a 
second  body. 

Also  with  alkalies,  Maly  found  that  if  bilirubin  were 
dissolved  in  dilute  soda  solution,  and  one  half  put  in  a 
tube  above  mercury,  the  other  left  open  in  a  dish  to  the  air, 
the  portion  left  open  to  the  air  became  brown  green  in  a 
few  days,  while  the  portion  cut  off  from  the  air  retained 
its  red  brown  colour  at  the  end  of  a  month.  If  a  few 
bubbles  of  oxygen  were  now  allowed  to  enter  the  tube 
with  the  quicksilver,  they  were  gradually  absorbed  and 
the  fluid  became  green. 

*  Phipson,  jfournal  of  the  Chemical  Society,  1867,  vol.  xx.  p.  458. 


42  Biliverdin. 

Another  solution  of  bilirubin  in  weak  soda  was  poured 
into  a  U  tube  with  one  end  sealed,  and  the  sealed  end 
completely  filled  with  the  fluid.  Here  one  end  only 
of  the  fluid  was  exposed  to  the  air ;  and  if  the  green 
colour  were  due  to  oxydation  from  the  air,  the  colour 
would  first  appear  at  that  end  which  was  exposed  and 
gradually  spread  by  the  bent  part  into  the  closed  tube. 
This  was  really  the  case. 

In  another  experiment  Maly  introduced  dry  bilirubin 
into  a  strong  glass  tube  within  which  were  a  few  glass 
globules  with  thin  walls  containing  dilute  soda  solution. 
The  glass  tube  was  drawn  out  into  a  fine  capillary  nozzle, 
bent  into  a  U  shape.  The  glass  tube  and  its  contents 
were  now  raised  by  means  of  a  water  bath  to  the  tem- 
perature of  23*1°  C.  The  capillary  tube  was  then 
quickly  sealed  with  the  blow-pipe.  The  globules  were 
now  broken,  and  in  a  few  days  the  fluid  became  green. 
The  tube  was  then  again  heated  to  23*  1°  and  the  end 
of  the  capillary  tube  broken  ofl"  under  water.  Water 
immediately  found  its  way  through  the  capillary  tube 
into  the  glass. 

These  experiments  show  that  the  oxygen  in  the  for- 
mation of  biliverdin  is  derived  from  the  air.  Indigo 
white,  gallic  acid,  and  pyrogallic  acid  behave  in  this 
way  just  as  bilirubin  does.* 

Besides  the  acids  and  alkalies,  Maly  finds  that  bro- 
mine and  iodine  have  also  an  action  upon  bilirubin, 
bromine  especially  so.  If  bilirubin  be  introduced  into  a 
bell  jar  in  which  moist  air  and  bromine  gas  are  present, 
the  bilirubin  soon  becomes  dark,  and  no  longer  soluble  in 
chloroform,  but  is  soluble  in  spirit  with  a  pure  green 
colour.  The  action  of  the  bromine  may  very  easily  go 
too  far,  so  it  is  better  to  use  the  following  method  :  a 
yellow  solution  of  bilirubin  in  chloroform  is  mixed  with 
a  few  drops  of  a  very  weak  alcoholic  solution  of  bromine. 

*  Maly,  Wien.  Silztmgsbb.  1868,  Bd.  Ivii.  Abth.  ii.  p.  99. 


Biliverdin.  43 

The  first  few  drops  make  the  fluid  dark  green,  and  the 
fluid  must  be  carefully  added  in  order  to  hit  the  point 
at  which  the  whole  fluid  becomes  a  fine  green. 

Nascent  oxygen  has  a  rapid  action  upon  bilirubin. 
If  a  little  binoxyde  of  lead  be  carefully  added  to,  and 
mixed  with,  a  freshly  prepared  alkaline  solution  of  bili- 
rubin, the  fluid  acquires,  before  two  minutes  be  over, 
the  green  brown  colour  which  bilirubin  has  after  it  has 
simply  stood  exposed  to  the  air  for  a  few  days.  If  a 
little  hydrochloric  acid  and  much  spirit  be  added,  there 
is  at  once  a  solution  of  biliverdin. 

Spongy  platinum  lessens  the  time  of  the  formation  of 
biliverdin  from  a  few  days  to  a  fewhours.  If  the  red  brown 
solution  of  bilirubin  be  placed  in  a  shallow  dish,  and 
spongyplatinum  thrown  in,  it  is  possible  to  see  the  change 
of  colour  pass  from  the  platinum  into  the  fluid  around. 

Permanganate  of  potash  gives  at  once  further  oxyda- 
tion  products. 

According  to  Maly  the  best  method  of  preparing 
biliverdin  is  as  follows :  Binoxyde  of  lead  is  slowly 
mixed  with  an  alkaline  solution  of  bilirubin  until  the 
fluid  give  a  pure  green  precipitate  with  acids.  The 
whole  of  the  fluid  is  then  faintly  acidified  with  acetic 
acid,  when  there  is  a  complete  precipitation  of  biliver- 
din-lead,  leaving  the  fluid  colourless  above.  The  pre- 
cipitate is  filtered  off,  washed  till  the  filtrate  be  free 
from  lead,  then  acted  on  by  alcohol  holding  sulphuric 
acid,  filtered  and  washed  with  water. 

Pure  biliverdin  is  a  black  shining  body,  but  when 
powdered  is  black  green.  It  is  without  taste  or  smell  and 
does  not  readily  become  wet  with  water.  When  heated 
to  100°  C.  it  gives  up  some  amount  of  water.  At  this 
temperature  it  remains  unchanged  in  weight,  but  after 
being  thus  dried  becomes  very  hygroscopic. 

The  purest  biliverdin  is  soluble  in  alcohol.  The 
solution  is  not  deep  green,  but  rather  sap  green.      As 


44  Bilifuscin. 

soon,  however,  as  a  trace  of  acid  be  added  (hydro- 
chloric, sulphuric,  or  acetic)  the  whole  becomes  of  a 
fine  green. 

If  to  the  alcoholic  solution  of  biliverdin  a  little 
ammonia  and  chloride  of  calcium  be  added,  a  dark 
green  precipitate,  insoluble  in  water,  is  thrown  down  : 
if  nitrate  of  silver  be  added,  a  dark  brown  precipitate  is 
thrown  down  in  flakes,  with  complete  decoloration  of 
the  fluid.  This  biliverdin-silver  is  not  soluble  in  water, 
but  is  easily  soluble  in  ammonia  with  dark  chestnut 
colour.  Biliverdin-lead  prepared  in  the  same  way  is  in 
brown  green  flakes. 

Rubbed  up  with  concentrated  sulphuric  acid,  bili- 
verdin is  dissolved  with  a  green  colour,  and  is  thrown 
down  unchanged  by  water,  in  green  flakes  which  are 
soluble  in  alcohol. 

In  caustic  alkalies  and  their  carbonates,  it  is  dis- 
solved with  a  sap  green  or  brown  green  colour.  It  is 
soluble  in  small  amount  in  aether,  and  not  in  chloro- 
form. If,  however,  the  chloroform  hold  a  little  alcohol, 
it  dissolves  the  biliverdin  readily.  It  is  also  soluble  in 
glacial  acetic  acid,  in  chloroform  and  glacial  acetic 
acid  mixed,  and  also  in  ordinary  strong  acetic  acid, 
with  remarkably  fine  colour. 

Biliverdin  is  not  soluble  in  benzol,  sulphide  of 
carbon,  very  slightly  soluble  in  amylic  alcohol  and 
iodine-sethyl,  but  if  these  two  bodies  contain  a  little 
sethylic  alcohol,  they  dissolve  biliverdin  with  ease. 

Methylic  alcohol  dissolves  biliverdin  as  readily  as 
ordinary  alcohol.* 

Bilifuscin.  It  seems  to  be  agreed  by  all  chemists  that 
bilirubin  and  biliverdin  are  present  in  the  bile,  and  are 
the  chief  colouring  matters  of  the  secretion.  Stadeler, 
however,   describes  a  series  of  pigments,  the   existence 

•  Maly,  Sitzungsbcyicfiie  d.  math.-naturw.  Classc  d.  kaiscrlichcn  Akademie, 
Wien,  1868,  Bd.  Ivii.  Abth.  ii.  p.  104. 


Biliprasin.  45 

of  which  is  not  admitted  by  others.  One  of  these  pig- 
ments is  biUfuscin,  which  Stadeler  finds  in  the  dark  brown 
green  residue  which  is  left  in  his  method  after  the  action 
of  hydrochloric  acid  upon  the  bilirubin  from  gall  stones. 
(See  page  28.)  Boiling  chloroform  dissolves  the  bili- 
rubin, and  the  extracts  are  at  first  dark  coloured,  and 
leave  by  evaporation  a  very  dark  residue,  which  liquifies 
in  the  heat  of  a  water  bath,  and  becomes  crystalline  on 
cooling.  If  this  mass  be  treated  with  absolute  alcohol, 
a  brown  pigment,  with  other  matters,  is  extracted. 
This  brown  pigment  Stadeler  calls  bilifuscin.  To 
obtain  it  out  of  the  alcoholic  solution,  the  fluid  is 
evaporated  to  dryness,  and  the  black  brown  residue 
treated  with  absolute  aether.  The  ^ther  takes  up  a 
part  of  the  pigment  and  the  palmitic  acid  and  other 
fatty  acids.  The  bilifuscin,  insoluble  in  the  aether,  is 
found  to  be  scarcely  soluble  in  chloroform.  It  is  an 
almost  black,  shining,  brittle  body,  which  in  powder  is 
almost  olive  green. 

With  nitric  acid  it  gives  the  same  play  of  colours  as 
bilirubin.  From  the  elementary  analysis,  Stadeler  gives 
the  formula :  C3^H^°N"0^  on  the  old  notation.  It  is 
therefore,  only  bilirubin  with  two  more  molecules  of 
water.     After  incineration  it  leaves  no  ashes. 

When  much  diluted,  the  solution  in  alcohol  shows 
the  same  colour  as  deeply  jaundiced  urine.  It  appears 
to  be  almost  insoluble  in  aether,  chloroform,  and  water. 
It  appears  to  be  soluble  in  alkaline  solutions  and  to 
form  a  compound  with  lime  as  bilirubin  does,  but  much 
less  bulky.* 

If  bilirubin  be  heated  with  hydrochloric  acid,  a  dark 
brown  appearance  is  formed,  due,  Stadeler  thinks,  to 
the  presence  of  his  bilifuscin. f 

Biliprasin.      Stadeler's  second  pigment,  biliprasin,  is 

*  Stadeler,  Arch.  d.  Chem.  n.  Pliarm.  1864.  Bd.  cxxxii.  pp.  326  and  337. 
f  Stadeler,  ibid.  p.  334. 


46  Bilihumin. 

got  when  the  residue  from  the  gall  stones  gives  no  longer 
any  brown  pigment,  and  acquires  a  bright  olive  colour. 
It  still  contains  much  bilirubin,  and  also  a  green  colour- 
ing matter,  biliprasin,  which  dissolves  in  alcohol  with 
a  fine  green  colour.  It  is  removed  by  repeated  treat- 
ment with  spirit,  and  then  the  bilirubin  completely 
extracted  with  boiling  chloroform.  To  prepare  the 
biliprasin  from  the  alcoholic  solution,  which  also 
contains  a  very  small  amount  of  bilirubin,  the  solution 
must  be  evaporated  to  dryness,  and  the  residue  pow- 
dered and  treated  with  aether  and  chloroform.  It  must 
then  be  dissolved  in  a  very  little  cold  spirit,  and  the 
filtered  deep  green  solution  evaporated  to  dryness.  The 
pure  biliprasin  remains  as  a  shining,  almost  black,  brittle 
crust,  like  bilifuscin  ;  when  powdered  it  has  a  greenish- 
black  colour.  It  becomes  fluid  on  being  heated,  shows 
bubbles  and  sends  off  peculiarly  smelling  vapours  which 
are  but  little  coloured.  When  incinerated  it  leaves 
about  0'6  per  cent,  of  ashes  of  weak  alkaline  reaction 
but  not  effervescing  with  acids.  The  formula  accord- 
ing to  Stadeler  is  C^^H^N'C  on  the  old  notation. 

Very  little  biliprasin  is  found  in  gall  stones.  It  is 
insoluble  in  water,  aether,  and  chloroform,  while  it  is 
easily  soluble  in  alcohol  with  green  colour.  The 
solution  of  biliprasin  becomes  brown  with  ammonia,  and 
this  distinguishes  it  from  biliverdin.  It  gives  a  fine 
play  of  colours  with  nitric  acid  ;  it  is  easily  soluble  in 
the  pure  alkalies,  but  less  in  the  carbonate  of  soda.  If 
acids  be  added  to  the  alkaline  solution,  the  green 
colour  returns,  and  the  solution  is  no  longer  brown. 
This  reaction  is  seen  in  jaundiced  urine.  Stadeler 
thinks  that  the  colour  of  this  urine  is  due  chiefly  to 
biliprasin.* 

Bilihumin  is  the  body  which  remains  behind  when 
the  gall  stones  have  been  treated  with   aether,  water, 

*  Stadeler,  Annalen  d.  Chcmic,  1864,  Bd.  cxxxii.  p.  339. 


Blue  Bile  Pigments.  47 

dilute  acids,  chloroform,  and  spirit.  In  order  com- 
pletely to  free  it  from  the  pigments  spoken  of  above,  it 
is  washed  with  ammonia  water,  and  remains  as  a  black 
brown  powdery  body.  Stadeler  made  no  elementary 
analysis  of  it  for  it  still  contains  epithelium  and  mucus, 
and  is  therefore  impure.  It  shows  a  play  of  colours 
with  nitric  acid. 

Blue  pigments  have  been  mentioned  by  several 
chemists  when  treating  of  the  constitution  of  the  bile. 
Stadeler,  in  speaking  of  the  products  of  the  oxyda- 
tion  of  bilirubin,  pointed  out  that  a  blue  pigment 
could  be  got  as  one  of  the  stages,  and  thought  it 
probable  that  this  blue  pigment  had  some  relation 
to  the  indigo  colouring  matter  of  the  urine.*  Maly 
likewise  described  more  in  detail  the  blue  product  of 
the  oxydation  of  bilirubin. t 

Ritter  has  described  a  blue  pigment  in  the  bile  of 
man,  oxen,  sheep,  pigs,  dogs,  and  cats,  and  which  he 
isolates  by  the  following  process  :  the  bile  is  filtered  and 
shaken  with  chloroform  ;  the  chloroform  is  separated  by 
decantation,  and  then  shaken  up  with  a  weak  solution  of 
soda  ;  this  is  afterwards  neutralised  with  hydrochloric 
acid  ;  the  two  layers  are  separated,  the  watery  holding 
the  blue  matter  in  suspension.  This  blue  pigment  is 
insoluble  in  chloroform  or  acids.  Its  alkaline  solution 
is  colourless  or  yellow.  The  only  difference  between 
the  new  body  and  indigo  is,  that  the  solution  of  the 
former  in  an  alkaline  glucose  fluid,  if  neutralized  by 
an  acid  and  exposed  to  the  air,  does  not  allow  a  red 
compound  to  be  deposited  until  a  few  days  be  over, 
or  even  as  much  as  a  month  ;  while  in  like  solutions  of 
indigo  the  colour  becomes  immediately  blue.:{: 

Jaffe  also  says  that  if  the  impure  solution  of  bilifuscin, 

*  Stadeler,  op.  cit.  p.  333. 

f  Maly,  Sitzungsbcyichte  d.  vtath.-fiattirw.   Classe  d.  k.  Akad.  d.  Wissenschaften, 
Wien,  1869,  Bd.  lix.  Abth.  ii.  p.  601. 

X  Ritter,  Bulletin  tnensuel  de  la  Societe  chimique  dc  Paris,  1870,  t.  xiii.  p.  212. 


48  Bilicyanin. 

which  is  obtained  when  the  chloroform  extract  of  gall 
stones  is  acted  on  by  absolute  alcohol,  be  acidified  and 
exposed  to  the  sunlight,  the  solution,  at  first  of  a  dirty 
brown,  passes  in  an  hour  or  two  into  a  fine  blue,  and 
this  without  any  intermediate  stage  of  green.  It  shows 
three  absorption  bands  in  the  spectrum,  but  Jaffe  has 
not  had  an  opportunity  for  further  study  of  the  body.* 

Bilicyanin.  Heynsius  and  Campbell  have  described 
the  changes  which  the  spectrum  of  the  bile  pigments 
undergoes  in  oxydation.  They  find  that  all  the  pigments 
which  Stadeler  describes  give,  when  oxydised,  a  violetblue 
pigment  which  at  first  shows  bands  at  C  and  E,  later 
only  one  band  at  F.  The  place  of  this  band,  therefore, 
agrees  with  that  described  by  Jafi"e.  The  same  body 
arises  also  by  the  action  of  other  oxydising  agents,  and 
it  was  possible  to  obtain  the  body  in  substance  by 
treating  bilirubin  with  bromine  water,  washing  with 
water,  shaking  up  with  chloroform,  and  evaporation  of 
the  extract.  Heynsius  and  Campbell  called  this  new 
body  bilicyanin  on  account  of  its  deep  blue  colour, 
it  appears  that  Stokvis  had  before  them  described  a 
body  identical  with  this,  but  named  it  choleverdin  ;t 
he  has,  however,  withdrawn  this  name,  and  now  uses 
only  bilicyanin.:]:  Heynsius  and  Campbell  find  that  if 
the  oxydation  of  bilirubin  by  means  of  nitric  acid  be 
allowed  to  proceed  so  far  that  only  the  band  at  F  be 
visible,  and  if  then  the  solution  be  thrown  into  a  large 
amount  of  water,  brown  flakes  of  choletelin  are  thrown 
down.  This  body  in  acid  solutions  shows  the  band  at 
F  ;  in  alkaline  solutions  it  does  not  immediately  show 
the  band  described  by  Jaffe  and  marked  with  d,  but  it 
does  show  it  after  the  addition  of  chloride  of  zinc,  with- 

♦  Jaffe,  Arch.f.  d.  gcs.  Phys.  1868,  Bd.  i.  p.  271. 

f  Stokvis,  Maandblad  v.  h.  Gcnootsch.  tcr  bcvord  van  uat.-  gen.-  en  heclk.  te 
Amsterdam,  1870.  s.  10.  I  have  not  seen  this  article.  I  borrow  the  reference 
from  Heynsius  and  Campbell. 

{  Stokvis,  Journal  of  the  Chemical  Society,  1873,  vol.  xxvi.  p.  288. 


Bilicyanin.  49 

out  the  exhibition  of  fluorescence.  This  choleteHn  they 
consider  identical  with  the  urobiHn  of  Jaffe. 

BiHcyanin  they  always  find  in  human  gall  stones, 
when  these  are  boiled  with  hydrochloric  acid  after  com- 
plete exhaustion  with  solvents.  It  is  never  found  in 
fresh  bile,  but  is  formed  quickly  in  the  alcoholic  extract 
by  standing  exposed  to  the  air.  Choletelin  was  found 
in  two  gall  stones,  very  often  in  jaundiced  urine  ;  bili- 
cyanin, however,  was  found  only  once  and  that  but  for 
a  short  time.* 

Dr.  Thudichum  has  given  many  spectra  of  derivatives 
ot  the  colouring  matters  of  the  bile,  which  he  describes 
and  names.  The  reader  is  referred  to  his  work  for 
further  information. "j*  Likewise  Stadeler  at  the  end  of 
his  essay  describes  certain  green  colouring  matters 
which  give  a  decided  Gmelin's  reaction. J 


*  Heynsius  and  Campbell,  Centralblatt  f.  d.  med.  Wiss,  1872,  p.  696. 
f  Thudichum,  Tenth  Report  of  the  Medical  Officer  of  the  Privy   Council,  Lond. 
1868.  p.  251. 

X  Stadeler,  op.  cit.  p.  348. 


t 


CHAPTER   III. 

The  Fats,    Salts,   Gases,  and  Other    Constituents 

OF  Bile. 

Cholestearin,  though  found  in  the  bile,  is  not  pecuHar  to 
it  as  the  bile  acids  are,  but  it  is  found  widely  distributed 
in  various  other  parts  and  fluids  of  the  body.  Full 
descriptions  of  it  may  be  found  in  the  chemical  hand- 
books, and  I  shall  therefore  not  attempt  to  give  an 
exhaustive  account  of  its  chemistry.* 

The  most  common  method  of  preparing  cholestearin  is 
from  gall  stones,  which  ordinarily  contain  a  large 
amount  of  this  body.  They  are  powdered  and  then  ex- 
tracted with  boiling  alcohol,  the  solution  being  filtered 
while  hot.  On  cooling,  the  cholestearin  separates  in 
crystals,  which  must  be  purified  by  being  dissolved  in  boil- 
ing alcoholic  solution  of  potash,  allowed  to  separate  on 
cooling,  and  again  washed  with  cold  alcohol  and  water. 
Last  of  all  they  must  be  again  dissolved  in  alcohol 
and  aether,  and  the  solution  allowed  to  evaporate  to 
crystallization.  In  this  wa}^  cholestearin  may  be  got 
from  the  alcohol  and  aether  out  of  which  the  bile  acids 
have  crystallised. 

Cholestearin  is  insoluble  in  water,  but  soluble  in 
boiling  alcohol,  in  aether,  chloroform,  and  benzol.  It 
crystallises  from  alcohol  in  flat  rhombic  tables  ;  from 
chloroform,  benzol,  and  aether,  in  anhydrous  shining 
fine  needles.      The  flat  tables   often  need  a  very  fine 

*  'A  name  was  first  given  to  the  crystalline  principle  of  gall  stones  by  Chevreul 
{Annates  de  Chemic  ct  dc  Physique,  iSi6,  t.  ii.  p.  346.)  He  called  it  cliolcsterine,  from 
XoXri  bile,  and  im^ios  solid.  To  my  mind  a  better  name  is  cholestearin,  from  ;^;<jX)j, 
bile,  and  rriu^,  fat,  as  it  is  by  no  means  the  most  important  part  of  the  solids  of 
the  bile,  but  is  only  the  fat  of  the  bile.  The  Germans  formerly  spelt  the  word  in 
this  way.     Of  late  they  have  followed  the  P^ench. 


Lecithin.  51 

opening  in  the  stage  of  the  microscope  to  allow  them 
to  be  seen. 

The  formula  for  cholestearin  is  C^^H'^0^  It  was 
shown  by  Berthelot  to  be  a  monatomic  alcohol.*  The 
olefiant  gas  of  the  series  is  cholestearilin,  C^^H'^^ ;  ob- 
tained by  the  action  of  strong  sulphuric  acid  on  choles- 
tearin. 

Cholestearin  fuses  at  145°  C.  and  can  be  sublimed  in 
sealed  tubes  without  change  at  36o°C.  Solutions  of  cho- 
lestearin have  a  levo-rotatory  action  on  polarised  light, 
for   yellow  Hght,   —34°;     for    red,    — 27°*5  ;    for  white, 

-39°-5-t 

Although  cholestearin  be  insoluble  in  water,  yet  it  is 
held  in  solution  in  the  bile  by  the  action  of  the  alkaline 
salts  of  the  bile  acids,  which,  like  soaps,  are  able  to 
dissolve  cholestearin. 

With  strong  sulphuric  acid  and  iodine  a  violet  colour 
is  given ;  with  chloroform  and  sulphuric  acid,  a  blood- 
red  colour,  changing  to  purple. 

Lecithin,  a  body  containing  phosphorus,  is  also 
found  in  the  bile.  Like  cholestearin  it  is  not  peculiar 
to  the  bile,  but  is  found  in  greater  abundance  in  the 
nervous  tissues.  By  some  it  has  been  thought  akin  to 
Oscar  Liebreich's  protagon.  It  is  also  found  in  the  yolk 
of  egg,  semen,  white  corpuscles,  and  serum,  accompanied 
by  cholestearin. 

After  yolks  of  egg  have  been  freed  from  fat  and 
cholestearin  by  means  of  aether,  they  are  extracted  with 
warm  absolute  alcohol.  This  alcoholic  extract  is 
concentrated  and  then  exposed  to  a  cold  of  —  io°C.  A 
precipitate  is  thrown  down  of  lecithin.  Another  method 
is  to  throw  down  the  alcoholic  solution  of  lecithin  with 
chloride  of  platinum  with  which  it  forms  crystals. 


*  Berthelot,  Annates  de  Chemie  et  de  Physique,  1859,  t.  Ivi.  p.  51. 
t  Hoppe-Seyler,  Arch.  f.  path.  Anat.  185S,  Bd.  xv.  p.  129. 

E  2 


52    ■  Neurin  or  Cholin. 

Lecithin  is  a  yellowish  mass,  not  crystalhne,  and  very 
hygroscopic  ;  though  insoluble  in  water,  it  swells  up  in 
water  and  becomes  white  and  milky.  It  is  insoluble 
in  acids  and  alkalies,  and  chloride  of  sodium.  Mihev 
dissolves  it  easily  ;  cold  alcohol,  a  little  ;  hot,  readily. 

By  boiling  with  bar3^ta  water,  lecithin  is  decomposed 
into  neurin  or  cholin,  glycerine-phosphoric  acid,  and 
stearate  of  baryta : 

Glycerin 
Lecithin.  Stearic  Acid,    phosphoric  acid.        Neurin. 

According  to  Diakonow,  lecithin  may  exist  in  com- 
bination with  each  of  the  three  fatty  acids  ;  as  distearin- 
lecithin,  dipalmitin-lecithin  and  diolein-lecithin.  He 
looks  upon  it  as  a  salt  of  distearyl-glycerin  phOvSphoric 
acid  in  combination  with  neurin  as  a  base.* 

Neurin  or  Cholin.  In  i84g'j*  Strecker  discovered  in  the 
bile  of  pigs  a  body  which  in  1862J  he  found  also  in  ox 
bile.  This  body  he  named  cholin  ;  and  it  is  prepared 
by  the  following  method :  Fresh  ox  bile  is  decomposed 
by  boiling  with  baryta  water  ;  by  this  the  greater  part 
of  the  colouring  matter,  mucus,  fat,  and  cholestearin  is 
thrown  down.  To  the  filtered  solution  much  hydrate  of 
baryta  is  added,  and  the  whole  is  boiled  for  about  12 
hours.  Sulphuric  acid  now  throws  down  both  the. 
baryta  and  the  cholalic  acid,  which  may  be  separated 
from  one  another  by  means  of  boiling  alcohol.  The 
filtrate  is  now  evaporated  on  a  water  bath,  and  so 
much  sulphuric  acid  added  as  to  drive  out  the  hydro- 
chloric acid  completely.  By  treating  the  remainder 
with  spirit,  the  sulphates  remain  behind  with  the 
taurin  and  a  part  of  the  sulphate  of  glycocoll.  The 
alcoholic  solution   is  evaporated   so  as  to   drive  off  the 

•  Diakonow,  Hoppe-Seyler's  Mcd.-Clicni.  Untcrsuchu)tf;cu,  Berlin,  1866-71,  pp. 
221  and  403. 

f  Strecker,  Aniialcn  d.  Chcinic  u.  Plianii.  1849,  Bd.  Ixx.  p  ig6, 
I  Idem,  ibid.  1862,  Bd.  cxxiii.  p.  353. 


Neurin  or  Cholin.  53 

ammonia  and  is  then  boiled  with  hydrate  of  Htharge. 
The  filtrate  is  freed  from  lead  by  sulphuretted  hydrogen 
and  after  evaporation  and  extraction  with  alcohol,  the 
solution  is  decomposed  with  a  little  hydrochloric  acid 
and  chloride  of  platinum  :  there  is  thrown  down  a  pre- 
cipitate of  a  body  formed  by  cholin  in  combination  with 
chloride  of  platinum. 

The  formula  for  this  is  C^H^^NO,  HCl  -f  PtCP. 
Cholin  when  free  would  be  an  ammonia  base  whose 
formula  would  be  C^H'^NO.  The  rational  formula  is  un- 
known; but  it  maybe  an  amylenoxyd-ammonia,  C5H'°0, 
NH^;  or  an  asthyloxyd-trimethylamin  C'H^O  DH^N. 

Cholin  is  with  difficulty  soluble  in  absolute  alcohol, 
but  readily  in  dilute.  Strecker  has  obtained  cholin  in 
combination  with  carbonic,  sulphuric,  nitric,  and  oxalic, 
acids. 

Both  Dybkowsky*  and  Baeyerf  believe  that  Strecker's 
cholin  is  identical  with  the  body  which  O.  Liebreich 
has  obtained  from  brain  substance  and  which  he  calls 
neurin.^ 

According  to  Wiirtz,  neurin  is  hydrate  of  trimethylox- 
sethylammonium§  which  is  changed  by  heat  into  tri- 
methylamin-glycol. 

Hydrate  of  trimethylox- 

^THYLAMMONIUM.  TrIMETHYLAMIN.  GLYCOL. 

cSh  }  n.  oh  =  {CW)m  +  c^H^  {  gg; 

It  would  seem  probable  that  it  is  the  lecithin  in. the 
bile  which  is  the  source  of  the  neurin  ;  for  lecithin 
easily  breaks  up,  and  one  of  the  products  of  its  decom- 
position is  neurin.  Trifanovsky,  however,  takes  an- 
other view,  and  believes  that  the  neurin  exists  in  the 
bile  in  some  combination  with  either  the  biliary  or  the 

*  Dybkowsky,  Journal  f. prak.  Chemie,  1867,  Bd.  c.  p.  153. 
f  Baeyer,  Annal.  d.  Chemie  imd  Pharin.  1866,  Bd.  cxxl.  p.  306. 
X  O.  Liebreich,  ibid.  1865,  Bd.  cxxxiv.  p.  29. 
§  Wiirtz,  Journal f.  prakt.  Chemie,  1868,  Bd.  cv.  p.  411. 


54  Organic  Salts  of  the  Bile, 

fatty  acids.*  Both  of  these  opinions  are  of  course  pure 
hypotheses. 

Organic  Salts.  Some  soaps,  salts  of  the  fatty  acids, 
palmitate,  stearate,  and  oleate  of  soda  are  found  in  the 
bile.  The  salts  of  these  acids  were  noticed  to  be 
present  in  the  bile  by  Tiedemann  and  Gmelin."|" 

Dogiel  has  noticed  the  presence  of  acetic  and  pro- 
pionic acid  in  the  fresh  bile  of  oxen.  The  bile  was  de- 
composed by  boiling  with  baryta,  the  baryta  and  cholalic 
acid  thrown  down  by  sulphuric  acid,  and  the  filtrate 
distilled.  An  acid  fluid,  smelling  of  butyric  acid,  came 
over.  This  product  of  distillation  was  neutralised  by 
baryta,  the  baryta  in  excess  removed  by  carbonic  acid, 
and  the  fluid  evaporated  to  crystallization.  Acetate 
and  propionate  of  baryta  were  formed. J  It  would 
seem  quite  possible  that  the  presence  of  acetic  and  pro- 
pionic acids  in  the  bile  may  be  products  of  decomposi- 
tion, due  to  the  process  employed. 

Urea.  Popp  finds  urea  a  constant  constituent  of  the  bile 
of  oxen  and  pigs.  His  method  is  to  dilute  the  bile  taken 
from  the  gall  bladder  immediately  after  death,  and  then 
to  precipitate  with  lead,  to  remove  superfluous  lead  with 
sulpheretted  hydrogen,  and  then  to  evaporate  the  filtrate 
to  dryness  on  a  water  bath.  The  residue  consists 
chiefly  of  acetate  of  soda  and  urea.§  Jacobsen,  how- 
ever, found  no  urea  in  human  bile  freshly  gathered  from 
a  biliary  fistula ;  in  one  specimen  a  trace  of  leucin  was 
found,  but  no  tyrosin.|| 

Leucin.  Berlin  found,  in  the  gall  bladder  of  a  Sarcoram- 
phus  papa,  a  kind   of  vulture,  crystals  which,  from  their 

•  Trifanovsky,  Arch.f.  d.  gcs.  Phys.  1874.  Bd.  ix.  p.  497. 

f  Tiedemann  and  Gmelin,  Rcchcrchcs  &c.  svr  la  Digestion,  Paris,  1826.  lere 
partie,  p.  89. 

+  Dogiel,  Journal  f.  prak.  Chcmic,  1867,  Bd.  ci.  p.  298. 

§  Popp,  Annalcn  d.  Chcmie  u.  Pharmacie,  1870,  Bd.  clvi.  p.  88. 

II  Jacobsen,  reported  by  Westphalen,  Dcntschcs  Arch.  f.  klin.  Med.  1873.  Bd. 
xi.  p.  603. 


Inorganic  Salts  of  the  Bile.  55 

shape  seen  under  the  microscope,  he  judged  to  be  formed 
of  leucin.*  As,  however,  no  chemical  tests  were  used  for 
the  further  identification  of  the  body,  much  stress  must 
not  be  laid  on  the  observation.  The  ova  of  nematoids 
were  found  in  the  mucus  of  the  bile. 

Sugar.  A  saccharine  body  is  said  by  some  writers  to 
have  been  found  in  the  bile  by  Macbride.*!*  And  after  the 
discovery  of  the  sugar-making  function  of  the  liver  by 
Claude  Bernard,  sugar  itself  was  found  in  the  bile. 
But  this  is  a  purely  post-mortem  phsenomenon,  for  if  the 
bile  be  examined  immediately  after  death,  no  sugar  can 
be  found.  The  appearance  of  sugar  in  the  bile  is  due 
to  endosmosis  from  the  liver  itself.^  This  applies  only 
to  health. 

Albumen  is  not  found  in  the  bile,  at  least  in  health. 
It  is  not  uncommon  to  find  it  in  the  bile  of  the  human 
gall  bladder  ;  but,  as  in  the  case  of  sugar,  it  is  most 
commonly  a  post-mortem'  appearance.  A  very  slight 
trace  of  some  albuminous  body  was  found  in  the  two 
first  specimens  of  fresh  human  bile  examined  by 
Jacobsen,  but  it  is  doubtful  if  they  were  not  impuri- 
ties.§  In  former  times,  the  mucus  which  is  found  in 
cystic  .bile  in  large  amount  was  taken  for  albumen.  || 

Inorganic  Salts.  There  is  nothing  peculiar  about 
the  alkaline  salts  of  the  bile.  Their  base  is  chiefly  soda, 
the  chloride  being  in  large  quantity,  then  phosphate 
and    carbonate;    there  are  also    present   phosphate    of 


*  Berlin,  Arch.  f.  d.  holldndischen  Bcitrdgc  znr  Natiir-  tend  Heilkunde,  Utrecht, 
1858,  Bd.  i.  p.  103. 

f  See  Plainer,  Ueber  die  Nattir  und  den  Nutzen  der  Galle,  Heidelberg,  1845,  p.  i. 
I  have,  however,  looked  through  David  Macbride's  Experimental  Essays  on  Medical 
and  Philosophical  Subjects,  Second  edit.  Lond.  1767,  especially  the  essay  on  fixed 
air,  but  I  have  not  found  the  statement  that  bile  contains  sugar. 

X  Claude  Bernard,  Legons  sur  les  proprictes  physiologiques  et  les  alterations 
pathologiques  des  liquides  de  Vorganisnie,  Paris,  1859,  t.  ii.  p.  207. 

§  Jacobsen,  loc.  cit. 

II  Thenard,  Memoires  de  Physique  et  de  Chemie  de  la  Societe  d'Arcncil,  1807,  t. 
i.  p.  56, 


56  Gases  of  the  Bile. 

lime  and  chloride  of  potassium  :  small  quantities  also 
of  magnesia  and  silica  have  been  found. 

The  presence  of  iron  has  been  noted  in  the  bile  from 
the  days  of  Cadet*  down  to  the  latest  researches  of  the 
last  year  or  tvvo.f  It  appears  to  be  in  exceedingly 
small  quantity ;  not  more  than  a  milligramme  in 
20  C.C 4 

Copper  also  would  appear  to  be  a  constant  consti- 
tuent of  the  bile,  in  very  small  traces.  It  seems  to 
have  been  first  found  by  von  Gorup-Besanez§  in  the 
bile,  a  year  after  copper  had  been  found  in  gall  stones 
by  Bertozzi.ll 

Gases.  The  gases  of  the  bile  have  been  studied  by 
Pfliiger,  but  only  in  two  instances.  The  gall  bladder  of  a 
freshly  killed  dog  was  opened  under  mercury,  and  the 
gases  estimated.  In  the  first  experiment  the  following 
was  the  result : 

Oxyg-en        ........         '2  per  cent. 

Carbonic  acid,  driven  out  by  phosphoric  acid      .  41  "7       ,, 

Carbonic  acid,  pumped  out  ....  I4"4       ,, 

Nitrogen     ........         -4       ,, 

In  the  second  experiment  the  result  was  different : 

Oxygen  ........     7ioiie 

Carbonic  acid,  driven  out  by  phosphoric  acid        .       -6  per  cent. 
Carbonic  acid,  pumped  out  .         .         .         .5-         ,, 

Nitrogen        ........       -6       ,, 

The  amount  of  bile  used  in  the  experiments  was  very 
small,  and  a  large  error  may  thus  have  crept  into  the 
figures. 5[ 

*  Cadet,  M'cmoires  dc  V Academic  royalc  dcs  Sciences,  Annee  1767.  Paris,  1770, 
p.  483. 

f  Kunkel,  Arch.f.d.ges.  Pliys.  1877.  Bd.  xiv.  p.  353. 

J  Marcet  found  in  a  man  who  had  made  a  practice  of  swallowing  clasp  knives 
•5  grain  of  prussian  blue  in  150  grains  of  bile;  while  in  150  grains  of  ordinary  bile 
only  "2  grain  were  found.     {Mtd.  Cliir.  Trans.  1823,  vol.  xii.  p.  63.) 

§  F.  von  Gorup-Besanez,  Heller's  Arch.  f.  phys.  und  path.  Chcinic,  1846. 
Jahrg.  iii.  p.  17. 

II  Bertozzi,  ibid.  iS^Sy  P-  225,  (wrongly  paged  522),  from  Polli's  Annali  di  Chimica, 
Milan,  1845,  p.  32. 

•I  Pfluger,  Arch./,  d.  gcs.  Phys.  i86g.  Bd.  ii.  p.  173. 


Gases  of  the  Bile. 


57 


A  lew  months  after  Pfliiger,  Bogoljubow  published  a 
series  of  estimations  of  the  carbonic  acid  contained  in 
the  bile  of  dogs,  and,  in  one  case,  of  a  sheep.  In  the 
first  analysis  the  bile  was  freshly  secreted  and  taken  at 
once  from  the  hepatic  duct. 

Carbonic  Acid  in   igo  C.C. 


Uncombined. 

Combined. 

Total. 

i. 

19-5 

37- 

56-5 

2. 

I7-I 

62-5 

79-6 

3- 

25-4 

4- 

12-3 

5- 

IO-5 

2-4 

12-9 

6. 

6-8 

7- 

5  "06 

8. 

I2-I 

9- 

3-i6 

•29 

3 '45 

lO. 

iS-6 

•6 

i6-2 

This  last  was  from  the  bile  of  a  sheep. 

The  amount  of  carbonic  acid  in  the  bile  is  especially 
noteworthy,  and  would  seem  to  show  that  some  is  made 
in  the  liver,  as  the  amount  is  greater  than  in  other 
secretions.  Bogoljubow  seems  to  think  that  the  freshly 
secreted  bile  holds  much  more  carbonic  acid  than  bile 
which  has  been  a  long  time  in  the  gall  bladder  :  and 
that  the  longer  the  bile  has  been  in  the  gall  bladder  the 
less  carbonic  acid  it  holds.* 

Noel  found  in  the  bile  of  a  dog  :t 

Oxygen         .         .  .         .     I  "22  per  cent. 

Carbonic  Acid       .         .         .     4'63        ,, 
Nitrog-en       .         .         '.         •     9"i3 

Hoppe-Seyler  finds  that  the  bile  taken  freshly  from 
the  liver  during  digestion  either  contains  no  absorbed 
oxygen,  or  that  it  holds  less  than  '^percent,  of  this  gas.  J 

*  Bogoljubow,  Centralblatt  f.d.  vied.  Wiss.  1869,  p.  657. 

f  G.  Noel,  Etude  generate  sur  les  variations  physiol.  dcs  gaz  dii  sang,  These  de 
Paris,  1876.     Quoted  by  Hoppe-Seyler. 

X  Hoppe-Seyler,  Phys.  Chemie,  Berlin,  1878,  p.  307. 


CHAPTER    IV. 

Physical  and  Chemical  Appearances  of  the  Human 

Bile. 

The  appearances  of  bile  seen  under  the  microscope 
are  unimportant  and  in  no  way  comparable  to  those 
of  the  urine,  the  organic  and  inorganic  sediments  of 
which  give  to  the  physician  such  valuable  information. 
The  first  person  who  studied  the  bile  with  the  aid  of 
the  microscope  appears  to  have  been  Achilles  Mieg, 
who,  in  a  letter  to  Haller,  says  that  he  found  nothing 
particular  in  some  ox-bile  that  he  had  looked  at  save 
round  shining  drops,  marked  at  their  edges,  which  he 
compares  to  those  seen  in  dried  gum.* 

Delius  not  only  described  the  appearances  seen  under 
the  miscroscope  in  bile  but  also  had  them  engraved. 
He  has  indeed  left  an  almost  exhaustive  account  of  what 
little  there  is  to  be  noted.  He  speaks  first  of  certain 
cubical  crystals  from  human  bile  which,  from  their 
pointed  ends  as  seen  in  the  plate,  and  the  arrangement  of 
their  square  surfaces  together,  might  be  set  down  as 
cylindrical  epithelium.  In  ox  gall  he  saw  but  few  of 
these  square  crystals,  but  abundance  of  granules  ar- 
ranged in  stellate  lines.  In  a  capon  he  found  rounded 
figures,  in  the  plate  they  look  like  oil  drops,  which 
Delius  says  were  of  a  violet  or  blue  colour.  In  the  bile 
of  fish  he  found  again  cubical  bodies  or  parallele- 
pipeds.t 

Weber  noted  also  certain  round  and  elliptical  globules, 
of  different  sizes,  in  general  small ;  and  smaller  than  those 

*  Achilles  Mieg,  Epistol.  ah  eruditis  viris  ad  Albert.  Hallcy  script,  pars  iv. 
Bernae,  1774,  vol.  iv.  p.  104. 

f  Henrici  Friderici  Delii  super  bile  humana  observationts  nonnullce  microscopico 
chcmica'  Epistola  ad  Gulielmum  Michaelum  Richterum,  Erlanga;,  1788.  It  is  con- 
tained in  Richter's  Circa  bills  naturam,  Erlanga;,  1788,  p.  xliv. 


The  Bile  seen  tinder  the  Microscope.  59 

seen  in  the  milk  and  mucus.*  Ducrotay  de  Blainville 
speaks  of  granules  like  fat,  spots  of  colouring  matter,  and 
occasionally  vibriones.t  These  vibriones  were  never  seen 
by  Bouisson  in  his  observations,  J  although  they  were 
detected  by  Charcot  and  Gombault  in  the  cystic  bile  of 
certain  animals  whose  bile  ducts  had  been  ligatured.  § 
Bouisson  says  that  the  bile  when  seen  under  the  micro- 
scope usually  presents  only  a  yellow  layer  ;  sometimes  a 
few  mucus  globules  and  tables  of  cholestearin.  Much 
the  same  remark  is  made  by  Fauconneau-Dufresne 
and  Mandl.jl 

Frerichs  describes  the  following  bodies  as  seen  under 
the  miscroscope:  (i.)  rounded  balls,  transparent  or  grey- 
ish, usually  grouped  together  and  removed  by  alcohol 
and  acetic  acid,  but  not  by  filtration.  (ii.)  Conical  yel- 
low bodies  joined  together  in  rows,  without  any  nucleus 
that  could  be  made  out.  (iii.)  Certain  bodies  not  peculiar 
to  the  bile,  to  wit,  black  or  dark  brown  granules,  which 
disappear  on  the  addition  of  caustic  potash  ;  apparently 
pigment  granules,  (iv.)  Rarely  small  crystals  in  colour- 
less rhombic  tables  of  cholestearin.^ 

In  Gorup-Besanez' description  of  the  bile  seen  under 
the  miscroscope,  he  divides  the  appearances  into  two 
heads  ;  those  constant,  and  those  variable. 

There  are  two  constant  appearances  :  (i.)  molecular 
granules,  very  like  coagulated  albumen,  only  yellow  or 
yellow  brown,  and  refracting  the  light  strongly.  He 
thinks  these  are  only  coagulated  mucus,  (ii.)  Epithe- 
lium of  the  gall  bladder  and  ducts. 


*  Weber,  Anatomie  des  Menschen,  Bd.  i.  p.  163.  quoted  by  Burdach,  Traite  de 
Physiologic,  Jourdan's  ed.  Paris,  1837,  ^-  '^''-  P-  44°- 

f  Ducrotay  de  Blainville,  Cours  de  phys.  gen.  et  camp.  Paris,  1829,  t.  iii.  p.    140. 

+  Bouisson,  De  la  bile,  Montpellier,  1843,  p.  23. 

§  Charcot  and  Gombault,  Archives  de  Physiologie,  1876,  p.  289. 

II  Fauconneau-Dufresne,    Traite  de  V affection   calculeuse  du  foie,   Paris,    185 1. 

P-  39- 

%  Frerichs,  Archiv.f.  phys.  21.  path.  Chemie,  1845.  p.  442. 


6o  The  Bile  seen  under  the  Microscope. 

The  variable  appearances  are  :  (i.)  Cholestearin  :  in 
100  cases,  the  rhombic  tables  peculiar  to  this  body  were 
onl}^  seen  three  times  ;  in  the  bile  of  cases  of  chronic 
Bright's  disease,  wasting  after  typhoid,  and  hypertrophy 
of  the  heart.  In  the  last  case,  the  bile  deposited  an 
abundant  sediment  of  shining  particles,  and  20  gall 
stones  were  already  present  in  the  gall  bladder.  (ii.) 
Crystals  of  margarin.  (iii.)  Drops  of  fat.  (iv.)  Taurin. 
(v.)  Blood  ;  the  bile  must  be  concentrated  to  show  the 
corpuscles:  if  thin,  it  dissolves  them  and  it  is  to  this 
that  the  solution  of  the  corpuscles  by  the  bile  is  to  be 
attributed,      (vi.)  Pus  corpuscles.* 

E.  Neumann  has  found  in  the  bile  of  a  man,  who  died  of 
pneumonia,  bodies  exceedingly  like  the  corpora  amylacea 
of  the  prostate.  They  were,  however,  much  smaller;  the 
largest  had  only  a  diameter  of  0*028  mm.  and  the  great 
number  were  not  nearly  so  large.  In  form,  they  were  some 
circular,  others  oval,  or  of  no  regular  shape,  but  showing 
a  three  or  four-pointed  figure  with  angles  rounded  off. 
They  all  showed  distinctly  concentric  rings.  In  the  centre 
of  most  was  a  small  cavity  from  which  rents  spread  out 
towards  the  circumference.  These  bodies  had  a  fatty 
look,  and  were  coloured  yellow,  apparently  from  the  bile. 
Iodine  coloured  them  green,  which  was  changed  into  a 
bluish  green  by  dilute  sulphuric  acid.  In  the  gall 
bladder  there  was  a  large  quantity  of  gall  stones. f 

The  temperature  of  the  bile  at  the  moment  of  its 
secretion  is  unknown. 

Some  observations  on  the  electricity  of  the  bile  were 
made  by  Bellingeri,  but  they  are  of  no  value  in  the 
present  state  of  knowledge.  J 

It  cannot  be  said  that  our  knowledge  of  the  properties 

*  Von  Gorup-Besanez,  Untcrsnchuiigen  i'lbcr  Galle,  Erlangen,  1846.  p.  28,  and 
Heller's  Archiv.f.phys.  u.  path.  Chcmie  u.  Microscopic,  1846.  Jahrg.  iii.  p.  i. 

f  E.  Neumann,  Arch.f.  viikros.  Anatomic,  1866,  Bd.  ii.  p.  510. 

+  Bellingeri,  Mcmovic  delta  rcalc  Accadcinia  dcllc  Scicnzc  di  Torino,  1827.  t. 
xxxi.  p.  314. 


Human  Bile.  6i 

of  human  bile  is  in  a  satisfactory  state.  The  earHer 
observations  both  on  men  and  brutes,  were  all  made  on 
bile  taken  from  the.  gall  bladder  after  death,  or  as  soon 
as  the  beasts  were  slaughtered.  Bile,  however,  which 
has  made  a  long  sojourn  in  the  gall  bladder  may  be 
looked  upon  as  dead  bile.*  It  contains  a  far  larger 
amount  of  solid  matter,  much  mucus,  and  has  lost  the 
property  of  changing  starch  into  sugar.  It  is  only  quite 
lately  that  an  attempt  has  been  made  to  study  more 
closely  the  properties  of  active  bile,  freshly  secreted  by  the 
liver.  This  has  again  and  again  been  done  in  animals 
since  the  method  of  making  biliary  fistulse  has  been 
found  out,  but  in  man  very  few  opportinuties  have  offered 
themselves  for  any  prolonged  investigation  of  this  sort  ; 
biliary  fistulse,  formed  by  disease  or  injury,  being  very 
rare ;  and  in  the  few  cases  known  it  is  only  in  two,  and 
and  these  published  within  the  last  ten  years,  that  any 
accurate  observations  have  been  made.f 

The  two  cases  to  which  I  refer  are  reported  by  H. 
Westphalenf  and  Johannes  Ranke.§  Westphalen's 
case  is  that  of  a  man  aged  32,  who  had  an  opening  made 
in  the  fifth  right  intercostal  space  for  an  empyema.  About 
400  C.C.  of  stinking  pus  came  out,  followed  some  days 
later  by  bile.  From  May  16.  to  May  30.  the  fasces  were 
colourless,  and  during  this  time  the  observations  were 
made. 

The  case  of  Johannes  Ranke  was  also  seen  in  a 
man,  aged  38,  in  whom  there  existed  a  communication 
between  the   bronchi  and  an  echinococcus   sac  in   the 

*  Dr.  Kemp  [Proc.  of  Royal  Society,  1856.  Vol.  viii.  p.  133.)  believes  that  the 
mucous  membrane  of  the  gall  bladder,  or  the  mucus  secreted  by  it,  decomposes 
hepatic  bile. 

f  An  early  attempt  at  the  examination  of  human  bile  is  mentioned  by  Haller 
{Elcin.  Phys.  Lugd.  Batav.  1764,  t.  vi.  p.  605.)  "  In  homine  cui  latus  apertum 
bilem  ex  vesicula  emittebat,  Cajetanus  Tacconus  cysticse  bilis  solius  4.  uncias 
vidit  eodem  tempore  fluxisse." 

X  H.  Westphalen,  Dcutches  Aych.f.  klin.  Med.  1873.  Bd.  xi.  p.  588. 

§  Johannes  Ranke,  Die  Blutvertheilung  u.s.w.  Leipzig  1871.  p.  144. 


62  Physical  Properties  of  Hitman  Bile. 

liver.  The  patient  brought  up  a  quantity  of  bile  by  the 
mouth,  but  it  is  a  matter  of  necessity  that  the  bile  thus 
offered  for  examination  should  be  impure ;  and  the 
inferences,  therefore,  drawn  from  its  examination  are 
less  trustworthy  than  those  taken  from  a  case  in  which 
the  fistula  opened  directly  upon  the  surface  of  the  body. 

In  Westphalen's  case  it  was  found  that  freshly  se- 
creted bile  was  of  bright  golden  yellow  colour,  and  it 
was  only  by  exposure  to  the  air  that  it  showed  the  well- 
known  changes  into  brown  and  green.  In  other  cases 
of  biliary  fistula,  the  colour  has  been  said  to  be  greenish 
yellow,*  greenish, f  grass  green,  J  or  greenish  brown. § 
The  belief  of  the  best  physiologists,  as  expressed  by 
Dr.  Lauder  Brunton,||  would  seem  to  accord  with  the 
statement  of  Westphalen. 

Westphalen  and  von  Wittich  both  found  the  bile  free 
from  viscidity.  Von  Wittich  examined  two  portions. 
The  first  was  clear  and  limpid.  The  second  not  so 
clear ;  and  after  standing  some  hours  showed  a 
change  in  colour  which  passed  into  yellow  brown,  and 
at  the  same  time  a  yellow  precipitate  was  thrown 
down. 

The  highest  specific  gravity  which  Westphalen  ob- 
served was  1016,  the  lowest  1008.  The  mean  of  22 
days'  observation  was  1010-4.  Johannes  Ranke's  mean 
was  1025,  but  the  sources  of  error  in  this  case  must  not 
be  forgotten. 

The  reaction  was  neutral  or  barely  alkaline,  accord- 
ing to  Westphalen  and  Jacobsen.      Von  Wittich  found 

*  MdicVhtT&on,  American  Jojirnal  of  Med.  Set.  i?>']i.  Vol.  Ixi.  p.  409.  Laboul- 
bene,  Union  mcd.  1875,  t.  xx.  p.  273. 

f  Grandclaude,  and  Dassit,  in  Fanconneau-Defresne's  Traitc  dc  Vaffeciion  cal- 
ciilcuse  du  foic,  Paris,  1851.  pp.  307.  and  311. 

X  John  Harley,  Med.  Chir.  Trans.  1866.  Vol.  xlix.  p.  89. 

§  Von  Wittich,  Arch.f.  d.  gcs.  Phys.  1872.  Bd.  vi.  p.  181.  An  account  of  this 
case  has  also  been  published  by  Hertz,  Berlin,  klin.  Woch.  1873.  p.  161. 

II  Lauder  Brunton,  in  Sanderson's //aH<^ioo/c /or  the  Pliysiological  Laboratory, 
Lend.  1873.  p.  495. 


Chemistry  of  Human  Bile.  63 

it  clearly  alkaline,  and  the  same  observer  has  shown 
that  fresh  human  bile  contains  a  ferment  which 
has  the  power  of  changing  starch  into  sugar.  This 
power  does  not  appear  to  be  enjoyed  by  bile  taken  after 
death  from  the  gall-bladder.* 

In  Johannes  Ranke's  case,  the  solids  of  the  bile  were 
found  to  vary  from  2*69  per  cent,  to  4'oi  per  cent.  In 
Westphalen's  case  the  mean  was  2'25  per  cent,  a  much 
lower  figure. t 

In  Johannes  Ranke's  case,  the  bile  acids  formed  40 
to  78-8  per  cent,  of  the  total  solids,  the  mean  being 
53 '45  P^i"  ^^^^^-  I'he  fats  with  cholestearin  from  4-8 
to  22'5  per  cent,  the  mean  being  14.48  per  cent.  The 
pigments  and  mucus  from  10-28  to  24*  11  per  cent,  the 
mean  being  17-29  per  cent.  The  ash  varied  from  13-1 
to  17-8,  the  mean  being  i^-jg  per  cent. 

These  figures  are  somewhat  different  from  those 
given  by  Jacobsen,  the  chemist  who  analysed  the  bile  of 
Westphalen's  case.     They  are  as  follows  : 

Of  the  organic  constituents,  3-14  jlj^r  c^;^/.  of  dry  bile 
was  soluble  in  anhydrous  aether  :  of  this  were  : 

Cholestearin 2.' \(^  per  cent . 

Fatty  matters    .....  '44      j> 

Lecithin    .         .         .         .         .         .  •21       „ 

The  lecithin  was  estimated  by  the  amount  of  phos- 

*  J.  Jacobsen  (quoted  by  von  Wittich,  Arch.f.  d  ges.  Phys.  1872.  Bd.  vi.  p.  182. 
from  an  inaugural  Diss,  de  sacchari  forviatione  fermentoqiie,  etc.  Regimont.  1865.) 
finds  the  same  power  in  the  fresh  bile  of  frogs^  pike,  carp,  sheep,  calves,  oxen, 
swine,  rabbits,  cats,  horses,  geese,  ducks,  and  fowls.  Only  once,  however,  did  he 
find  it  in  human  bile,  apparently  taken  from  the  gall  bladder  after  death. 

f  In  the  lower  animals  the  amount  of  solids  seems  to  vary  much  in  different 
tribes.  Thus  Bidder  and  Schmidt  found  that  the  fresh  secretion  of  the  liver  of 
cats,  dogs,  and  sheep,  gave  an  average  of  5  per  cent,  of  solids  ;  of  rabbits,  hardly 
2  per  cent. ;  but  of  geese  and  crows  j  per  cent.  The  contents  of  the  gall  bladder  in 
cats,  dogs,  and  rabbits  gave  10  to  20  per  cent,  of  solids ;  but  of  sheep  not  more  than 
8  per  cent.  In  geese,  the  amount  of  solids  was  from  10  to  20  per  cent. ;  in  crows  it 
was  as  high  as  25  per  cent.  (Bidder  and  Schmidt,  Die  Verdauiingssdfte,  Mitau  and 
Leipzig,  1852.  p.  214.)  The  fresh  bile  of  guinea  pigs  holds,  according  to  Heiden- 
hain,  not  more  than  i'35  per  cent,  and  does  not  give  a  reaction  with  Pettenkofer's 
test  [Arch.f.  Anat,  Phys.  u.s.w.  i860,  p.  648.) 


64 


Chemistry  of  Human  Bile. 


phorus.  The  bodies  insoluble  in  aether  and  alcohol, 
probably  coloured  mucin,  made  up  lo  per  cent,  of  the 
solids. 

The  alcoholic  extract  of  dry  bile  contained : 


Glycocholate  of  soda 
Palmitate  and  stearate  of  soda  . 


44"  8  per  cent. 
6-4      „ 


that  is  51*2  per  cent,  of  dry  bile. 

Jacobsen    gives   the    following   table    of  the  amount 


of  the  inorganic  constituents : 


Per  Cent,  of 
Ashes. 

Per  Cent,  of 
Dry  Bile. 

Per  Cent,  of 
Fluid  Bile. 

Chloride  of  potassium 

Chloride  of  sodium 

Carbonate  of  soda 

Phosphate  of  soda 

Phosphate  of  lime 

3-39 
65-16 
ii'ii 
15-90 

4-44 

1-276 

24-508 

4-180 

5-984 
1-672   . 

0-029. 

0-557- 

0-095. 

0-136. 

•038. 

loo-oo 

37-620 

0-855. 

The  bile  contained  not  a  trace  of  sugar  or  of  any 
other  body  which  would  reduce  copper.  Urea  was 
not  present.  Only  in  the  first  tested  specimens  were 
traces  of  albuminous  bodies  and  of  leucin  found,  but 
no  tyrosin  was  ever  discovered.  Quinine  and  mercury 
were  also  not  found  in  the  bile  when  they  were  looked 
for,  apparently  after  being  administered  by  the  mouth. 

Of  the  better  known  biliary  pigments  bilirubin  and 
biliverdin  were  detected.  Copper  could  always  be 
found  in  traces  in  the  ash  of  the  bile. 

By  decomposing  the  soda  salts,  soluble  in  alcohol 
with  hydrate  of  baryta,  glycocoll  only  was  formed,  and 
not  a  trace  of  taurin.  The  absence  of  taurocholic  acid 
could  also  be  directly  ascertained,  as  the  dried  bile  was 
completely  free  from  sulphur. 

This  statement  is  contrary  to  the   common   belief  of 


Human  Cystic  Bile.  65 

physiologists.  Taurocholic  acid  is  said  by  Dr.  Lauder 
Brunton  to  be  the  chief  acid  in  human  bile.* 

Jacobsen  later  on  found  taurocholic  acid  in  the  bile 
from  the  gall  bladders  of  persons  dying  of  various 
diseases,  in  one  case  even  as  much  as  14*2  per  cent,  of 
the  dry  bile.  The  bile  also  contained  small  quantities 
of  iron,  silica,  magnesia,  and  a  trace  of  copper. f 

The  bile  taken  after  death  from  the  gall  bladder  of 
healthy  men  killed  by  accident  was  examined  years  ago 
by  FrerichsJ  and  von  Gorup-Besanez§  whose  papers 
appeared  almost  at  the  same  time.  Analyses  of  the 
bile  of  persons  dying  of  diseases  not  connected  with  the 
liver,  have  been  more  lately  made  by  Trifanovsky||  and 
Socoloff.^l 

Frerichs  describes  healthy  bile  from  the  gall  bladder 
as  always  being  of  a  full  brown  colour,  in  thin  layers 
brownish  yellow,  never  green.  In  old  persons  it  is 
darker.  Its  consistence  is  watery  and  thin  ;  only  in 
the  last  drops,  or  in  the  bile  of  new  born  children  is  a 
viscid  appearance  seen :  von  Gorup-Besanez  thinks 
that  the  colour  of  the  healthy  bile  may  pass  through  all 
shades  of  colour,  from  pale  yellow  to  black ;  and  that 
the  consistence  may  be  that  of  tar,  or  thin  as  water. 

The  specific  gravity,  according  to  Frerichs,  was  in 
three  cases  1040 ;  in  one  only  1032.  Von  Gorup- 
Besanez  has  made  no  observations  himself  on  the 
specific  gravity,  but  quotes  John,  Schiibler,  and  Kapff 
as  finding  it  1026.  Bouisson  also  gives  the  same 
figure.** 

*  Lauder  Brunton,  loc.  cit. 

t  Jacobsen,  Berichte  d.  deutschcn  chem.  Gesellschaft,  1873.  Bd.  vi.  p.  1026. 

X  Frerichs,  Hannoversche  Annalen,  1845.  Jahrg.  v.  p.  42.  Also  in  Heller's 
Archiv  f.  phys.  und  path.  Chemie,  1845.  p.  442. 

§  Von  Gorup-Besanez,  Heller's  Archiv  f.  phys.  and  path.  Chem.  1S46.  Jahrg. 
iii.  p.  I.  and  Untersuchungen  iiber  Galle,  Erlangen  1S46. 

II  Trifanovsky,  Arch.f.  d.  ges.  Phys.  1874.  Bd.  ix.  p.  492. 

II  Socoloff,  ibid.  1876.  Bd.  xii.  p.  54. 

**  Bouisson,  de  la  Bile,  Montpellier.  1S43.  p.  13. 

F 


66 


Human  Cystic  Bile. 


The  smell  of  the  bile  is  said  by  von  Gorup-Besanez 
to  be  peculiar :  disgusting,  and  like  the  smell  of  human 
faeces.  In  my  own  opinion  this  is  by  no  means  common, 
and  the  human  bile  has  rather  an  aromatic  smell. 
The  taste  is  notoriously  bitter.  The  reaction  was 
found  in  von  Gorup-Besanez'*  two  first  cases  to  be 
neutral,  and  this  appears  to  be  the  case  more  often 
than  that  the  reaction  is  alkaline. 

The  results  of  Frerichs'  analysis  of  the  bilS  of  two 
healthy  young  men  in  a  percentage  are  as  follows  : 

Water         .... 

Solids      '     .         .         .         . 

Soda  salts  of  the  bile  acids 

Cholestearin 

Marg-arin  and  olein     . 

Mucus  .         .         .         . 

Chloride  of  sodium 

Phosphate  of  soda 

Phosphate  of  lime  and  magnesia 

Sulphate  of  lime 

Oxyde  of  iron 

Gorup-Besanez  gives  the  following  analyses  :J 


Aged  i8. 

86-00 
14-00 

Aged  22. 
85-92. 

14-08. 

.       '        7-022f 

•16 

9-14. 
•26. 

•32 

2-66 

•92. 
2-98. 

•25 

•2. 

•2 

a            -18 

•25- 

•28. 

•02 
Traces 

•04. 

Traces 

Water 

Solids 

Bile  Acid  Salts      .     . 

Fats 7 

Oiolestearin  .  .  ) 
Mucus  with  Pigment 
Inorganic  Salts     .     . 


Man    Aged  49 
Beheaded. 


822-7 

loyg 
47'3 

22-1 

IO-8 


Woman  Aged  29 
Beheaded. 


loi-g 
56-5 
30-9 

14-5 
6-3 


Man   Aged   68 
Death  by  Ac- 
cident. 


908-7 
91-3 

737 
17.6 


Boy  Aged   12 

Death  from 

Wound. 


828-1. 
171-9. 

148-0. 
23"9- 


In  two  foetal  twins  of  six  months,  Frerichs  found  the 
meconium,  which  he  looks  upon  as  little  else  but  foetal 
bile,  to  have  the  following  composition  when  dried  : 

*  Von  Gorup-Besanez,  Uutcrsrichiingcii,  u.s.w.  p.  44. 
f  In  the  original  it  stands  70-22.     Clearly  a  printer's  mistake. 
X  E.    F.  von    Gorup-Besanez,  Lclirh.  d.   Cliciiiic,   Braunschweig,   1862.  Bd.   iii. 
p.  469. 


Human  Cystic  Bile. 


67 


Cholestearin,  olein,  and  margarin  . 

1-8 

I5-4- 

Biliary  resin  (bile  acids) 

12-3 

15-6. 

Epithelium,    mucus,    pigment   and 

salts 

85-9 

69-00 

Frerichs  thinks  the  foetal  bile  poor  in  biliary  salts, 
but  rich  in  carbon,  as  the  liver  is  almost  the  only 
organ  (?)  by  which  carbon  can  escape  during  foetal  life. 

Trifanovsky,  under  Hoppe-Seyler's  direction,  has 
made  analyses  of  the  bile  taken  after  death  from  the 
human  gall  bladder.  A  quantity  of  bile,  529'6ii 
grm.  was  collected  from  the  bodies  of  those  who  died 
of  any  disease  whatever ;  and  a  second  quantity, 
306*628  grm.  from  those  whose  livers  were  found  free 
from  disease.  The  bile  was  poured  from  the  gall 
bladder  into  a  vessel,  filled  with  two  thirds  of  alcohol, 
and  so  protected  from  decomposition.  The  results  of 
the  analysis  are  as  follows : 


Water         ... 

90-878. 

91-079. 

Solids          .         .       ■ . 

9-122. 

8'92i. 

A.  Insoluble  in  spirit 

2-8o8. 

1-636. 

I.  Soluble  in  water  and 

Ash. 

Ash 

acetic  acid 

0-134. 

•082. 

0-323. 

•12, 

2.  Mucus  and  phosphate 

of  iron 

2-674. 

•191. 

I-3II- 

•013 

B.     Insoluble    in    absolute 

alcohol     . 

0-846, 

1-82. 

I .     Before    precipitation 

with  aether 

0-76.  ^ 

1-723. 

•514 

2.  After  precipitation 

-       -442. 

with  aether 

o-o86.^ 

0-097. 

•06 

C.  Soluble  in  absolute  alcohol 

I.  Taken  up  by  aether    . 

0-835. 

1-023. 

a.  Cholestearin 

0-251. 

0-335- 

b.  Lecithin          .         .  ) 

c.  Fat         .         .         .; 

0-017. 

0-524. 

0-359- 

d.  Soap 

•06. 

0-312, 

2.  Precipitated  by  aether 

4-633- 

4-444. 

F  2 

68  Human  Cystic  Bile. 

The  precipitate  thrown  down  by  aether  is  commonly 
looked  upon  as  made  up  of  bile  acids,  though  it  certainly 
contains  soap  and  alkaline  salts.  Trifanovsky  divided 
it  into  several  parts,  and  estimated  in  one  the  amount 
of  sulphur,  in  the  second  the  alkalies,  in  the  third  the 
chlorine,  in  the  fourth  the  nitrogen,  and  lastly  the 
amount  of  cholalic  and  fatt}^  acids. 


Cholalic  acid      .         .         .         . 

Palmitic,  stearic,  and  oleic  acids 

Sodium  as  metal 

Potassium  as  metal 

Sulphur       .         .         .         .         . 

Chlorine     ..... 

Nitrosfen    ..... 


49753.  38-842; 

15-095.  27-46. 

3-619.  2-135. 

I -106.  4"586. 
•93-  2-5. 

?  1-33. 

?  4-69. 

But  the  total  amount  of  these  bodies,  estimated 
separately,  is  considerably  less  than  the  amount  given 
by  the  first  analysis  ;  so  there  must  remain  in  solution 
in  the  aether  some  body  which  makes  up  the  balance. 
And  this  is  the  case  ;  it  is  a  body  rich  in  nitrogen, 
either  ammonia  or  some  organic  base,  not  glycocholic 
or  taurocholic  acid.  In  reality,  an  organic  base  was 
procured  in  combination  with  chloride  of  platinum 
from  the  acid  filtrate  which  was  obtained  by  throwing 
down  the  cholalic  acid  with  hydrochloric  acid  from  its 
combination  with  baryta.  From  this  filtrate  there 
were  obtained  a  few  crystals  of  taurin  and  a  little  amor- 
phous substance  which  still  contained  glycocoU.  The 
combination  with  platinum,  which  was  very  soluble  in 
water,  showed  crystals  which  suggested  by  their  shape 
and  colour  some  neurin  compound  ;  and  this  was  veri- 
fied by  its  amount  of  platinum;  -162  grm.  of  crystals 
gave  '052  grm.  of  platinum.  A  compound  of  platinum 
with  neurin  in  purity  would  give  •0516  grm.  of  platinum. 

It  has  been  stated  that  neurin  is  present  in  human 
bile.  According  to  Trifanovsky  it  does  not  arise  from 
a  decomposition  of  lecithin,  but  is  more   probably  con- 


Human  Cystic  Bile.  69 

tained  as  some  combination  with  the  bile  acids  or  some 
fatty  acids.* 

Socoloff,  dissatisfied  with  all  that  had  been  done 
before  him,  determined  to  make  a  fresh  analysis.  He 
assumed  that  the  bile  was  quite  natural  when  taken 
after  death  from  the  bodies  of  persons  whose  disorder 
brought  in  its  train  no  appreciable  disease  of  the  liver  ; 
an  assumption  which  will  not  pass  unchallenged.  He 
made  six  analyses  in  the  following  manner :  the  bile 
was  evaporated  at  a  low  temperature,  and  the  solid 
matters  extracted  with  absolute  alcohol  till  the  filtrate 
became  quite  colourless.  This  alcoholic  extract  was  eva- 
porated to  a  small  amount,  and  then  sether  added  until 
a  precipitate  were  no  longer  thrown  down.  After  two  or 
three  days  the  aether  was  poured  off  and  the  precipitate 
once  more  dissolved  in  alcohol,  and  thrown  down  with 
sether  ;  and  this  procedure  repeated  so  long  as  a  preci- 
pitate could  be  seen  and  the  aether  remained  colourless. 
In  this  way,  bile  acid  salts  with  chloride  of  sodium  and 
potassium  are  found  in  the  precipitate  with  aether. 
Further,  Socoloff  estimated  in  these  salts  the  amount 
of  sulphur,  after  Liebig's  method,  by  fusing  with  potash 
and  nitre. 

The  mixture  of  alcohol  and  aether,  containing  the 
soaps,  fats,  cholestearin,  and  lecithin,  was  distilled, 
the  residue  dried  at  a  low  temperature  and  completely 
extracted  with  anhydrous  aether.  What  was  insoluble 
in  aether  was  looked  on  as  soap  :  what  was  soluble  in 
anhydrous  aether  was  held  to  be  fat,  cholestearin,  and 
lecithin. 

*  Trifanovsky,  Arch.  f.d.  gcs.  Pliys.  1874.  Bd.  ix.  p.  492. 


70 


Human  Cystic  Bile. 


Age  and  Sex  of  Patient. 
Cause  of  Death. 


Solids  insoluble  in  ab- 
solute alcohol .     .     .     . 

Precipitate  with  sether, 
i.e.  bile  acids  and  chlo- 
rides of  sodium  and 
potassium 

Sulphur 

Taurocholic  acid  .     .     . 

Taurocholate  of  soda. 

Soap 


Middle 

Young 

Man  aged 

Man     a- 

Aged  Man 

Man. 

50. 

BOUT  50. 

Cerebral 

Bright's 

Pleurisy 

H.^MOR- 

Disease. 

Phthisis, 

Heart 

AND     Em- 

rhage. 

No  Disor- 

Liver Hy- 

Disease, 

physema, 

Liver  Hy- 

der  OF 

VZKJEUIC. 

Liver  Hy- 

Liver  Hy- 

PER.EMIC. 

Liver. 

per.-emic. 

PER/EMIC. 

4-801 

4-111 

1-520 

3-749 

3-292 

8-993 

4-263 

3-819 

6-278 

9-794 

•144 

-071 

•o5i 

-0S9 

-II 

2-324 

I-I43 

•928 

1-449 

1-782 

2-431 

I-197 

1-031 

1-506 

1-865 

1-524 

2-082 

1-303 

1-320 

1-046 

TWO  Biles 

USED. 

One  of 
Phthisis, 
OTHER    of 

Heart 
Disease; 


4-875. 

5-679 
•081 

I-317 
1-376 
1-442 


These  figures   represent  the  amount  per  cent,  in  fluid 
bile. 

By  this  table  it  will  be  seen  that  human  cystic  bile 
suffers  many  variations  in  its  quantitative  composition. 
The  precipitate  with  aether  is  that  which  is  most  vari- 
able ;  though  the  sulphur,  and  therefore  the  taurocholic 
.acid,  is  most  constant.  Its  mean  was  23*833  per  cent. 
of  the  precipitate  with  aether.  The  amount  of  soap 
was  also  nearly  the  same  in  all.*  Ernst  Bischoff  and 
Lossen  have  made  six  estimations  of  the  amount  of 
sulphur  in  human  bile,  and  they  find  the  mean  to  be 
i-^per  cent.  The  amount  varied  however  from  '83  to  2*99 
per  cent.  Like  Socoloff,  they  find  that  glycocholic  acid 
is  the  more  abundant  acid  in  human  bile.f  Kiilz,  who 
employed  a  modification  of  Carius'  method  of  esti- 
mating the  sulphur,  has  in  one  analysis  found  only 
•1358  per  cent,  of  sulphur,  an  exceedingly  low  figure. 
Much  the  same  amount  was,  however,  found  in  the 
bile  of  sheep,  pigs,  calves,   and  oxen. J 

*  Socoloff,  Arch.f.d.  ges.  Phys.  1876.  Bd.  xii.  p.  54. 

t  Ernst  Bischoff,  Zcilschrift  f.  rat.  Med.  1864.  Bd.  xxi.  p.  147. 

X   Kiilz,  Arch./.  Aiinf.  Phys.  u.s.w.  1872.  p.  98. 


Summary  of  Knowledge  of  Human  Bile.  71 

To  sum  up,  then,  our  present  knowledge  of  the  phy- 
sical and  chemical  characters  of  human  bile :  The 
appearances  seen  under  the  microscope  are  unimpor- 
tant ;  freshly  secreted  bile  is  a  fluid,  not  viscid,  of  a 
golden  yellow,  brown,  or  green  colour ;  its  reaction  is 
usually  neutral,  sometimes  barely  alkaline  ;  its  specific 
gravity  about  loio.  It  contains  about  2  to  3  per  cent. 
of  solid  matter  and  has  the  power  of  changing  starch 
into  sugar.  This  power  is  lost  if  the  bile  remain  long 
in  the  gall  bladder ;  it  then  shows  a  deeper  colour,  is 
brown,  and  is  of  a  higher  specific  gravity,  1030  to  1040, 
and  becomes  viscid  from  the  presence  of  mucus.  The 
amount  of  solids  in  this  cystic  bile  varies  from  8  to  17 
per  cent,  but  the  relation  of  these  solid  constituents  to 
one  another  does  not  seem  to  vary. 

The  soda  salts  of  the  bile  acids  make  up  about  one 
half  of  the  solid  constituents  ;  they  may,  however,  vary 
from  40  to  yo  per  cent,  of  the  solids.  It  is  known  that 
these  bile  acids  are  formed  by  a  combination  with  gly- 
cocoll  and  taurin,  but  whether  the  cholalic  acid  of  man 
be  identical  with  the  cholalic  acid  of  the  ox  is  not  known. 
It  is  certain  that  a  taurocholic  acid  exists  in  the  bile  of 
man,  although  now  and  then  it  may  be  entirely  absent, 
the  glycocholic  acid  being  usually  the  dominating  acid. 
This  forms  about  three  quarters  of  the  soda  salts  of  the 
bile  acids,  while  taurocholic  acid  forms  the  remaining 
quarter. 

It  is  known  that  bihrubin  and  biliverdin  exist  in 
human  bile  ;  the  other  bile  pigments  have  not  been 
found.  Their  amount  has  not  been  directly  estimated. 
With  mucus,  it  is  thought  to  be  from  10  to  15  per  cent. 
of  the  solids. 

The  fatty  matters,  the  cholestearin,  the  soaps,  and 
lecithin,  make  up  from  3  to  20  per  cent,  of  the  solids. 
They  seem  to  vary  inversely  with  the. amount  of  inor- 
ganic salts.     The  salts  may  be  from  15  to  35  per  cent. 


72  Summary  of  Knowledge  of  Human  Bile. 

of  the  solid  bile  ;  and  of  these  salts,  about  two  thirds 
are  made  up  of  chloride  of  sodium.  The  remainder 
consists  of  phosphate  of  soda  and  lime,  possibly  a  pro- 
duct of  the  lecithin,  carbonate  of  soda,  chloride  of 
potassium,  traces  of  magnesia  and  silica,  and  constantly 
traces  of  iron  and  copper. 

Urea,  sugar,  leucin,  tyrosin,  and  albumen  are  not 
found  in  health  in  human  bile.  Lecithin  and  neurin  are 
found,  but  it  is  not  known  if  the  neurin  exist  in  combina- 
tion, or  be  a  product  of  the  decomposition  of  the  lecithin. 

The  gases  of  human  bile  have  not  been  examined. 


As  this  page  was  passing  through  the  press,  I  found 
that  a  research  had  been  published  quite  lately  as  to 
the  composition  of  the  cholalic  acid  of  human  bile. 
Hammarsten  of  Upsala,  asserts  that  human  bile  con- 
tains bilirubin  and  hydrobilirubin,  and  that  the  bile 
acid  is  chiefly  a  glycocholic  acid  ;  but  the  cholalic  acid 
of  this  is  quite  different  from  the  cholalic  acid  of  oxen 
or  swine.  Bayer  corroborates  this  statement,  and  gives 
Qi8p^28Q4  ^g  ^]^g  formula  of  human  cholalic  acid.* 


*  Hammarsten   and  Bayer,   in  Maly's   Jahresbei'icht  ncbev  die   Fortsclirittc  d. 
Tliierchemie  f.  1878.     Bd.  viii.  p.  260.     Wiesbaden,  1879. 


CHAPTER   V. 

History  of  the  Physiology  of  the  Bile  :    the 
Sources  of  the  Bile  in  the  CEconomy. 

It  would  seem  to  us,  who  live  in  the  present  age, 
that  the  secretion  of  bile  would  be  the  first  function 
of  the  liver  to  become  known.  We  must,  however, 
go  back  to  the  early  records  of  medicine  to  see  if 
this  were  really  the  case.  And  in  few  matters  is  it 
more  clear  that  several  hands  had  a  share  in  the 
collection  of  books  which  we  call  Hippocrates  than 
in  the  teaching  about  the  humours  of  which  the  body 
is  composed.  The  writer  of  the  book  De  Morbis  Lib.  i. 
teaches  that  all  diseases  arise  from  two  sources,  bile 
or  phlegm,*  while  the  writer  of  De  natura  hominis  in- 
sists that  there  are  four  humours,  the  blood,  the  phlegm, 
the  yellow  bile,  and  the  black  bile,t  the  proper  balance 
of  which  in  the  body  is  health,  disease  arising  when 
there  is  excess  or  defect  of  any  of  these  humours.  On 
the  other  hand,  the  writer  of  De  Morbis  Lib.  iv.  teaches 
also  that  there  are  four  humours  ;  but  in  his  system 
the    black   bile    is    replaced  by   the    dropsy,    or  water. 

In  the  undoubted  writings  of  Hippocrates  there  is  but 


*  De  Morbis,  Lib.  j.  cap.  ij.  and  De  aff.  cap.  i.  Littre's  ed.  t.  vj.  pp.  143.  and 
208. 

f  De  nai.  horn.  cap.  iv.  Littre's  ed.  t.  vj.  p.  39.  The  four  humours  followed 
the  four  seasons,  and  it  is  likely  that  they  have  some  relation  to  the  four  elements. 
See  Sir  Thomas  Browne  on  the  number  four  (Pseiidodoxia  Epidcmica,  Bk.  iv. 
chap.  12.  Lond.  sec  ed.  1650.  p.  178.) 

X  Petersen  [Hippocratis  nomine  quae  circumferiintiir  scripta  ad  temporum  rationes 
disposita,  Hamburg,  1839,  p.  37.)  however,  notes  that  Plato  in  the  Tiiiicrus,  one  of 
his  undoubted  works,  speaks  of  the  four  humours,  while  in  other  dialogues  he  speaks 
only  of  bile  and  phlegm. 


74  History  of  the  Opinions  held     . 

little  information  as  to  what  is  meant  by  bile.*  It  is  a 
fluid,  yellow  and  bitter,t  formed  from  fat,:|:  seen  indeed 
in  the  upper  part  of  the  digestive  canal, §  but  also  found 
in  the  head  and  chest. ||  It  would  seem  doubtful  if  the 
yellow  bile  were  anything  more  than  some  fluid  or  se- 
cretion that  was  yellow  and  bitter  without  any  connexion 
with  the  liver  ;  thus  a  yellow  appearance  of  the  back  of 
the  tongue,  with  a  bitter  taste,  would  be  set  down  as  a 
bilious  disorder.  And  it  is  not  till  we  come  to  De  Morbis 
Lib.  iv.  that  we  find  any  suggestion  as  to  the  source  of 
the  bile.  Speaking  of  the  four  humours  which,  it  has 
been  said,  are,  according  to  this  writer,  blood,  phlegm, 
water,  and  bile,  he  says  the  blood  is  from  the  heart,  the 
phlegm  from  the  head,  the  water  from  the  spleen,  the 
bile  from  the  spot  which  is  upon  the  liver. 51  Later  on 
the  same  writer  says  :  "  Now  I  will  speak  of  the  bile, 
how  and  why  it  grows  in  the  body,  and  how  the  part 
which  is  upon  the  liver  draws  it  to  itself.  This  is  how 
it  is  :  If  a  man  have  eaten  or  drunken  something  that 
is  bitter,  or  perhaps  bilious  and  light,  and  the  bile  be- 
comes more  abundant  in  the  liver,  forthwith  the  liver 
suffers,  which  the  children  call  cardia ;  and  we  have 
seen,,  and  it  is  plain  to  us  that  it  comes  from  the  food 
and  drink  :  for  the  body  draws  to  itself  from  the  food 
all  of  the  aforesaid  humours  :  and  the  place  which  is  on 
the  liver  draws  to  itself  all  that  is  bilious."** 


*  It  is  plain  that  bile  must  have  been  talked  about  long  before  Hippocrates; 
the  word  x'^^  '^^''  cognates  in  the  Sanscrit,  Latin,  Teutonic  and  Slav  languages. 
The  porta  of  the  liver  was  also  the  part  inspected  in  the  sacrifices,  so  that  it  is 
likely  that  the  gall  bladder  and  its  contents  would  early  become  known.  The 
heart  was  inspected  as  well  at  a  much  later  date. 

f  Hippocrates,  dc  veteri  medicina,  cap.  xix.     Littre's  ed.  t.  i.  p.  619. 

X  Epidem.  Lib.  vj,  Sect.  v.  §  8.  Littre's  t.  v.  p.  319.  See  also  Sect.  vi.  §  i. 
p.  323.  Liebig  revived  the  notion  that  bile  was  formed  from  fat  (See  Animal 
Chemistry,  Lond.  1842.  p.  148.) 

§  De  diaeta  in  acutis,  cap.  g.     Littre's  ed.  t.  ij.  p.  295. 

II  De  diaeta  in  acutis,  cap.  11.     Littre's  ed.  t.  ij.  p.  311. 

H  De  Morhis,  Lib.  iv.  cap.  33.     Littre's  ed.  t.  vii.  p.  544. 

•*  De  Morbis,  Lib.  iv.  cap.  36.     Littre's  ed.  t.  vii.  p.  550. 


as  to  the  Physiology  of  the  Bile.  75 

Aristotle,  in  his  History  of  Animals ^  has  noted,  with 
considerable  accuracy,  the  tribes  in  which  the  gall 
bladder  is  absent.  Stags,  he  says,  have  no  gall 
[bladder],  but  they  have  a  colour  in  their  tail  which 
resembles  gall ;  although  their  intestine  is  so  bitter  that 
dogs  will  not  eat  it,  unless  the  stag  be  very  fat.  So 
also  the  livers  of  elephants  are  without  gall  [bladders]  ; 
yet  if  cut  into,  a  bilious  fluid  will  come  out.* 

In  another  place  he  says  that  the  livers  of  those  ani- 
mals that  have  no  gall  [bladders]  are  well  coloured  and 
sweet.  And  of  those  that  have  gall,  that  part  of  the 
liver,  which  is  under  the  gall,  is  most  sweet.  But  those 
animals  which  have  a  liver  not  well  tempered  have  also 
blood  less  pure ;  and  hence  the  excrement  which  is 
called  gall  is  secreted  from  them.  And  a  little  further 
on  he  says  :  Gall  therefore  is  alone  the  excrement  of 
the  liver. f 

The  views  of  Galen  are  also  very  obscure  as  to 
the  place  where  the  bile  is  secreted.  He  reprobates 
the  opinion  of  Asclepiades  that  the  yellow  bile  was 
formed,  not  separated,  in  the  bile  passages,  J  and  speaks 
of  the  gall  bladder  as  collecting  the  bile  ;§  and  that  it 
receives  the  secretion,  and  casts  it  forth  again. (|  But 
in  another  passage  he  compares  the  functions  of  the 
spleen  and  the  gall  bladder  in  purifying  the  blood  ;  the 
former  purging  it  of  the  black  bile  ;  the  latter  of  the 
bilious  and  serous  humours.^ 

Aretaeus  seems  to  have  taught  that  both  the  liver 

*  Aristotle,  History  of  Animals,  Book  ii.  chapt.  xv.  Taylor's  trans.  Lond.  iSog, 
p.  58.  Doves  have  no  gall  bladders ;  and  it  is  from  this  fact  that  they  are  the 
emblems  of  guilelessness. 

f  Aristotle,  On  the  movement  of  animals.  Book  iv.  Chapter  ii.  Taylor's  trans. 
p.  114. 

%  Galen,  De  nat.fac.  Lib.  i.  cap.  xiii.     Kiihn's  ed.  vol.  ii.  p.  40. 

§  De  anat.  admin.  Lib.  vi.  Cap.  viii.     Kiihn's  ed.  vol.  ii.  p.  569. 

II  De  nat.fac.  Lib.  iii.  cap.  xiii.  and  in  Hipp.  lib.  de  aliment,  com.  Lib.  iii.  cap. 
xxiii.     Kiihn's  ed.  vol.  ij.  ji.  187  and  vol.  xv.  p.  352. 

IT  De  atra  bile,  Cap.  viii.     Kiihn's  ed.  vol.  v.  p.  140. 


76  Views  of  Sylvius. 

and  the  gall  bladder  were  concerned  in  the  secretion  of 
bile  :  he  says  that  if  the  liver  be  inflamed  or  scirrhous, 
but  remain  unchanged  as  to  its  function,  then  it  be- 
gets (r/xm)  bile  in  the  liver ;  and  the  bladder  which  is 
in  the  liver  separates  (SiscKpivst)  it,*  but  if  the  passages 
which  convey  the  bile  to  the  intestine  be  obstructed,  then 
jaundice  is  caused.  Here  is  more  clearly  expressed,  of 
which  one  finds  many  traces  elsewhere,  the  doctrine  that 
in  the  liver  the  bile  is  formed,  with  the  urine,  black  bile, 
and  blood  ;  but  that  the  function  of  the  gall  bladder  is 
to  separate  and  collect  the  bile,  just  as  the  kidneys  and 
spleen  separate  and  collect  the  urine  and  black  bile. 

The  teaching  of  Avicennaf  would  seem  to  be  much 
the  same  as  that  of  Aretaeus.  He  says  that  the  blood 
is  formed  in  the  liver ;  and  in  it,  the  bile  and  black  bile-, 
and  watery  humour  {i.e.  the  urine)  are  separated  :^  and 
that  the  gall  bladder  draws  to  itself  the  subtle  humour 
proper  to  it  with  the  yellow  bile. 

Phineas  Fletcher's  Pirr/)/^  Island  is  a  treatise  in  rhyme 
on  the  physiology  of  this  little  kingdom,  man:  and  the 
opinions  set  forth  in  it  may  be  taken  as  the  popular 
belief  in  the  days  just  before  Harvey.  In  it  the  liver, 
not  the  gall  bladder,  is  indicated  as  the  seat  of  the 
secretion  of  the  bile.§ 

Yet  immediately  after  the  Harveian  Revolution, 
strange  doctrines  began  to  be  taught  as  to  the  source 

*  Aretaeus,  On  the  causes  and  symptoms  of  chronic  diseases,  Book  i.  chapter  xv. 
Adams'  ed.  p.  324. 

f  Avicenna,  Opera,  Lib.  iii.  fen.  14.  tract.  \.De  anatomia  hepatis,  Venetiis,  1608, 
Lib.  i.  p.  750.  and  p.  791. 

\  I  have  read  somewhere,  I  think  in  Daremberg's  Histoire  dcs  Sciences  medicalcs, 
that  Albert  and  S.  Thomas  have  strange  views  on  the  functions  of  the  liver.  It 
would  be  ill  work  looking  into  two  such  voluminous  schoolmen  without  some  guide; 
but  I  have  found  only  two  references  to  the  word  jeciir  in  the  ample  index  prefixed 
to  the  Venice  ed.  1595  of  S.  Thomas  ;  the  views  of  Albert  in  the  treatise  de  somno 
ct  vigilia  (Tract  ii.  cap.  iii.  ed.  Lugd.  1651.  t.  v.  p.  75.)  seem  to  be  mferely  that  the 
liver  is  the  seat  of  the  natural  spirits,  as  the  head  is  of  the  animal,  and  the  heart 
of  the  vital. 

§  Phineas  Fletcher,  Purple  Island,  Canto  iii.  Cambridge,  1633.  p.  29.. 


Views  of  Sylvius.  77 

of  the  bile.  De  Back,  a  physician  of  Rotterdam,  set 
forth  that  the  bile  was  not  made  by  the  liver,  but  by 
the  coats  of  the  gall  bladder.*  Sylvius  propounded 
the  same  doctrine,  but  more  at  length  :  he  says  that 
the  bile  is  formed  from  the  blood  brought  by  the  cystic 
arteries  to  the  gall  bladder,  and  thence  by  the  coats  of 
the  gall  bladder  it  penetrates  into  the  cavity.  From 
the  gall  bladder  it  descends  into  the  ducts  ;  by  the 
hepatic  duct  it  ascends  into  the  liver,  and  thence  passes 
to  the  heart ;  by  the  common  duct  it  passes  into  the 
intestine. "j" 

This  doctrine  of  Sylvius  was  supported  by  Vieussens 
who  says  that  he  has  demonstrated  by  experiment  that 
the  gall  bladder  is  the  only  part  of  the  body  destined 
to  separate  the  bile  from  the  blood ;  J  and  according 
to  Haller,§  the  doctrine  must  have  survived  into  the 
middle  of  the  eighteenth  century.  Morgagni,  too,  con- 
sidered it  necessary  to  prove  that  obstruction  of  the 
cystic  duct  did  not  cause  jaundice. || 

Perverse  as  this  teaching  seems,  there  is  yet  some- 
thing beyond  it.  G.  E.  Stahl  says  that  there  had 
been  some  who  did  not  acknowledge  that  the  bile  was 
secreted  by  the  body  generally,  and  then  at  last  excreted 
by  the  liver ;  but  who  had  persuaded  themselves  that 
the  bile  was  formed  from  the  more  subtle  parts  of  the 
food,  and  ascended  into  the   gall   bladder  through  the 

*  Jacobi  de  Back,  Diss,  de  corde,  Cap.  vj.  Lond.  1660.  p.  379.  The  edition 
which  I  have  seen  is  bound  up  and  paged  with  Harvey's  Exercitationes,  Lond. 
1661. 

t  Sylvius,  Praxeos  Med.  Lib.  i.  cap.  xliv.  §§  ii.  and  iii.  Op.  med.  Amstelod.  1679. 
p.  296.  The  Oxford  editor  of  Nemesius,  a  Bishop  of  Emessa  in  the  fourth  centurv, 
says  in  his  preface  that  the  doctrine  of  Sylvius  as  well  as  that  of  the  circulation  of 
the  blood  was  anticipated  by  Nemesius.  I  do  not  think  that  either  claim  holds 
good. 

+  Raymond  Vieussens,  Traite  nouveau  dcs  liqueurs  du  corps  humain,  Toulouse, 
1715-  P-  355- 

§  Haller,  Elein.  P/iys.  Lugd.  Batav.  1764.  t.  vj.  p.  587.  I  have  not  been  able  to 
see  the  authors  whom  Haller  quotes. 

II  Morgagni,  de  sedibus  etc.     Epist.  xxxvii.  §  10. 


78  Source  of  the  Bile 

common  duct.*  I  have  not  found  this  theory  anywhere 
but  in  Stahl. 

Malpighi  did  great  service  for  the  physiology  of  the 
liver  and  the  bile  ;  he  pointed  out  that  the  liver  was  a 
conglomerate  gland,  made  up  of  hexagonal  or  polygonal 
acini,  not  a  mere  mass  of  blood,  as  was  once  believed  ; 
that  the  bile  duct  was  the  excretory  duct  of  the  liver, 
as  the  ducts  of  the  parotid,  pancreas,  &c.  are  to  those 
glands  ;  that  the  bile  was  made  in  the  liver  and  passed 
into  the  intestines  by  the  duct.t 

For  the  last  hundred  years  it  has  been  the  undis- 
turbed belief  of  physiologists  that  the  bile  is  excreted  by 
the  liver,  and  not  by  the  gall  bladder  or  ducts. 

Source  of  the  bile. — It  was  the  opinion  of  Liebig  that, 
in  man  and  herbivorous  animals,  the  bile  was  formed 
chiefly  from  the  elements  of  the  food  which  contain  no 
nitrogen. J  It  was  thought  that  the  formula  of  cho- 
lalic  acid  (C'+H^^O^)  showed  its  kindred  to  the  fats. 
Redtenbacher  found  capric,  caprylic,  and  valerianic 
acids  amongst  the  products  of  decomposition  of  cho- 
loidic  acid.§  Von  Gorup-Besanez  thought  choloidic 
acid  and  cholic,  i.e.  cholalic  acid,  but  links  in  the  chain 
of  the  decomposition  of  the  fats  :||  and  it  was  a  favour- 
ite theory,  some  five  and  thirty  years  ago,  that  the  bile 
was  derived  chiefly  from  the  decomposition  of  the  fats  ; 
in  fact,  a  return  to  a  much  older  belief  that  the  bile  was 
a  kind  of  soap.^  Lehmann  noted  that  the  portal  vein 
held  a  large  quantity  of  fat,  which  had  disappeared  in 
the  blood  of  the  hepatic  vein,  and  he  thought  that  this 


*  G.  E.  Stahl,  Physiolog.  Sect.  j.  membr.  vii.  Arct.  iv.  De  bilis  secretione. 

f  Marcelli  Malpighii,  Dc  viscerum  strncturd  exercit.  nnat.  Londini,  i66g.  De 
Hepatc,  cap.  vii.  is  a  refutation  of  de  Back  and  Sylvius. 

X  Liebig,  Animal  Chemistry,  Lond.  1842.  p.  168. 

§  Redtenbacher,  Annalcn  d.  Clicmic  tttid  Pharm.  1846.  Bd.  Ivii.  p.  166, 

II  Gorup-Besanez,  ibid.  1846.  Bd.  lix.  p.  158. 

II  It  has  already  been  noted  (p.  74.)  that  Hippocrates  thought  bile  was  formed 
from  the  fat. 


from  the  Food  or  Tissues.  79 

fat  might  serve  in  the  secretion  of  bile.*  Bidder  and 
Schmidt,  however,  noticed  that  upon  an  exclusive  diet 
of  fat,  the  secretion  of  bile  at  once  fell  to  the  level  of 
that  in  an  animal  from  whom  all  food  was  withdrawn  ; 
so  that  they  think  that  the  nitrogenous  elements  of 
the  food  must  be  looked  on  as  the  chief  source  of  the 
bile.f  H.  Nasse,  in  his  earlier  work,  saw,  however,  a 
great  increase  of  the  secretion  of  .bile,  when  with  fat 
nitrogenous  foods  were  also  given. J  And  a  theory 
might  be  built  upon  these  observations  :  the  fats  might 
be  thought  to  furnish  the  cholalic  acid,  while  the  albu- 
minous bodies,  by  their  decomposition  into  taurin  and 
glycoco.ll,  gave  these  bodies  to  unite  with  the  cholalic 
acid  and  thus  .  form  the  conjugate  acids.  This  theory 
is  Kiithe's  ;§  and  it  is  undoubtedly  very  plausible  ;  but 
the  facts  on  which  it  is  founded  hardly  bear  it  out ; 
Ritter,  a  pupil  of  Nasse,  made  observations  on  the 
results  of  a  fatty  diet,  but  did  not  obtain  any  striking 
results. II  No  deductions  can,  in  my  opinion,  be  drawn 
from  his  figures :  and,  as  far  as  I  can  make  out,  Nasse 
is  the  only  observer  who  has  noticed  much  increase  of 
bile  on  mixed  fatty  and  flesh  diet. 

Frerichs  suggested  the  idea  that  the  bile  might  be 
formed  from  the  starchy  parts  of  the  food  ;5|  and  Kiithe 
also  supports  this  notion  by  pointing  out  that  if  from 
four  equivalents  of  starch,  enough  oxygen  be  taken,  the 
formula  of  cholalic  acid  remains.** 

*  Lehmann,  Physiological  Chemistry,  Day's  trans,  vol.  ij.  p.  87. 

f  Bidder  and  Schmidt,  Die  Verdanimgssdfte  und  der  Stoffwechsel,  Mitau  and 
Leipzig,  1852.  p.  236. 

X  Nasse,  Commentatio  de  bilis  quotidie  a  cane  secreta  copia  et  indole,  Marburg, 
1851.  p.  14. 

§  Kiithe,  Ztir  Function  der  Leber,  in  Heynsius'  Stud.  d.  phys.  Inst,  zu  Amster- 
dam, Leipzig  and  Heidelberg,  1861.  p.  24. 

II  Ritter,  Einige  Versuche  ueber  die  Absonderungs-Grosse  der  Galle  von  d.  Nah- 
rung.  Diss.  Inaug.  Marb.  1862.  p.  33. 

IT  Frerichs,  in  Wagner's  Handworterbuch  d.  Physiologic,  Braunschweig,  1846. 
Bd.  iii.  p.  831. 

**  Kiithe,  op.  cit.  p.  22. 


8o  Connexion  of  Bile  with  Glycogen. 

4  eq.  of  starch  C-''H^<'0^^ 

I  eq.  of  cholalic  acid  O'W0\ 

Ritter,  however,  found  that  in  a  dog  fed  only  on 
potatoes,  or  on  potatoes  and  fat  only,  the  amount  of 
bile  daily  secreted  fell  very  low.* 

The  amount  of  nitrogen  in  glycocoll,  and  of  nitrogen 
and  sulphur  in  taurin  would  certainly  seem  to  point  to 
an  origin  in  the  albuminous  bodies  of  the  blood  or 
food.t  Some  part  of  these  bodies  is  thought  to  be 
split  up  in  the  liver  into  taurin  and  glycocoll,  while  an- 
other part  goes  to  form  leucin,  tyrosin,  xanthin,  and 
hypoxanthin,  bodies  containing  nitrogen.  Meissner 
would  probably  go  a  step  further,  and  say  that  urea 
also  was  formed  abundantly  in  the  liver.  Do  the 
peptones  at  once  furnish  these  nitrogenous  bodies,  or 
are  they  derived  from  the  products  of  the  decomposition 
of  the  tissues  ?  Karl  Voit  would  answer  that  the  bile 
acids  are  derived,  like  urea,  from  the  tissues, J  while 
the  great  dependence  of  the  bile-making  functions  upon 
the  glycogenetic  function  would  seem  rather  to  suggest 
that  they  come  immediately  from  the  splitting  up  of 
the  peptones. 

Kiithe  has  suggested  an  ingenious  hypothesis  as  to 
the  relations  of  the  bile  to  the  making  of  glycogen, 
which  may  be  conveniently  spoken  of  here.  He  found 
that  when  the  bile  is  diverted  from  the  intestine,  no 
glycogen  is  formed  in  the  liver  ;  for  example,  when  a 
biliary  fistula  is  set  up  ;  or,  as  later  experiments  have 
shown,  when  the  common  duct  is  tied.  Also  in  Moos' 
experiments  of  tying  the  portal  vein,  no  bile  and  no 
sugar  was  found  in  the  liver  twenty-four  hours  alter  the 
operation.     By  tying  the  portal  vein,  the  return  of  bile 

•  Joseph  Franz  Ritter,  np.  cit.  p.  32. 

f  See  a  paper  by  A.  Froehde  in  Erlenmeyer's  Zcitsclivift  f.  Cliciiiic  unci  PJinr- 
iiiacic,  1864,  Jahrf(  vij.  p.  464. 

J  Karl  Voit,  Phys.-Chcm.  Unlcrsuchuugcn,  Augsburg,  1S57.  P-  4'^- 


Kiithe^s  Hypothesis.  8i 

from  the  intestines  to  the  Hver  by  the  blood  would  be 
stopped.  Is  it  possible,  then,  that  the  circulation  of  the 
bile  is  needful  for  the  making  of  glycogen  ?  Kiithe  thought 
perhaps  that  the  glycogen  might  take  its  source  from  the 
glycocoll  and  taurin  of  the  conjugate  acids.  To  prove 
this,  food  was  withheld  from  a  dog  for  5  days,  so  that  all 
the  glycogen  might  disappear  from  the  liver ;  then  5 
grammes  of  glycocoll  were  given  in  water,  and  the  dog 
was  killed  in  2^-  hours.  Sugar  and  glycogen  were  found 
in  the  liver.  Also  with  taurin  the  like  was  seen.  A 
dog  was  kept  without  food  or  drink  for  8  days  ;  and  on 
the  gth  day  4  grammes  of  taurin  in  water  were  given  to 
him,  and  the  dog  was  killed  in  2|  hours.  The  liver 
held  a  good  deal  of  glycogen  and  sugar,  while  sugar 
was  present  in  the  blood  of  the  carotid. 

Kiithe  sets  forth  from  this  the  following  propositions  : 
that  the  bile-making  function  is  the  chief  function  of  the 
liver ;  and  that  the  glycogenetic  is  subsidiary  to  the 
biliary  function  ;  diabetes  mellitus,  therefore,  depends 
upon  a  greatly  increased  secretion  of  bile,  while  artifi- 
cial diabetes  depends  upon  an  increased  change  of 
glycogen  into  sugar.  At  the  same  time  that  glycogen 
is  formed,  urea  is  formed  also.* 

Kiithe's  master,  Professor  Heynsius,  says,  on  the 
contrary,  that  he  does  find  glycogen  in  the  livers  of 
dogs  in  whom  a  biliary  fistula  has  been  set  up.  Out 
of  three  dogs,  it  was  not  present  in  one,  but  plainly 
present  to  the  glacial  acetic  acid  test  in  two  others, 
while  iodine  gave  a  negative  reaction  in  two,  and  a 
dubious  reaction  in  the  third.  Heynsius,  however, 
allows  that  diverting  the  bile  from  the  intestine  greatly 
decreases  the  amount  of  sugar  in  the  liver.     Heynsius 


*  Kiithe,  passim. 

Mead  {A  Mechanical  Account  of  poisons,  Lond.  1747,  4th  ed.  p.  32.)  says  that 
diabetes  is  much  akin  to  jaundice,  and  is  a  distemper,  not  of  the  kidneys,  but  of  the 
liver,  proceeding  from  a  vitiated  mixture  of  the  bile. 

G 


82  Place  of  llic  Secretion  of  Bile. 

also  found  that  the  length  of  time  for  which  Kiithe  kept 
his  dogs  without  food  was  not  enough  completely  to 
free  the  liver  from  glycogen.  Some  small  amount  still 
remains  at  the  end  of  a  week's  fast,  and  this  amount 
was  not  increased  by  giving  glycocoll  or  taurin  to  the 
animal  shortly  before  death.* 

If  these  experiments  of  Heynsius  prove  correct,  it 
will  undoubtedly  cause  Kiithe's  theory  of  the  forma- 
tion of  glycogen  solely  from  glycocoll  and  taurin  to  be 
abandoned.  Not  so,  however,  his  views  of  the  de- 
pendance  of  the  bile  and  glycogen  making  functions  of 
the  liver  upon  each  other.  Bernard  once  thought  them 
totally  distinctf  and  was  followed  by  writers  who  held 
that  some  cells  of  the  liver  secreted  the  one,  and  others 
the  other.  The  two  functions  have  undoubtedly  a  close 
relation  to  one  another ;  for  the  ligature  of  the  duct,  or 
the  diverting  of  the  bile  from  the  intestine,  causes  a 
great  decrease  of  glycogen  in  the  liver,  if  not  an  entire 
absence  from  that  organ. 

Secretion  or  only  Excretion  by  the  Liver. — In  the 
seventeenth  century,  Glisson  taught  that  the  liver  was 
a  mere  filter,  by  which  the  bile  was  strained  off  from  the 
mass  of  the  blood.  The  business  of  the  liver,  he  says, 
is  to  take  up  by  the  porta  the  blood  charged  with  bilious 
humours,  to  separate  the  bile,  and  then  to  return  the 
blood  made  pure  again  into  the  cava.  J  This  doctrine 
prevailed  quite  into  our  own  times,  and  was  specially 
favoured  by  physicians  to  whom  it  very  conveniently 
furnished  a  theory  of  jaundice  by  suppression  of  se- 
cretion. After  Budd,  the  doctrine  was  thought  to  be 
exploded,   but    it    was    revived   by   Liebermeister,   who 


*  Heynsius,  D/e  Quelle  des  LcbcrzHckcrs,\n  Stud.  d.  phys.  Inst,  zu  Amsterdam, 
Leipzig,  and  Heidelberg,  1861,  p.  57. 

f-  Claude  Bernard,  Ler,ons  sur  les  propriclcs  etc.  des  liquidcs  de  rorganisine,  Paris, 
1859,  t.  ii.  p.  203. 

I  Francisci  Glissonii,  Anatomia  Hcpalis,  Cap.  xli.  Amstelaedami,  1659,  p.  456. 


Place  of  the  Secretion  of  Bile.  83 

pointed  out,  quite  truly,  that  the  physiological  demon- 
stration of  the  secretion  of  the  bile  by  the  liver  was 
wanting.* 

The  theory  of  the  formation  of  the.  bile  in  the  body  at 
large  was  indeed  thought  to  be  disproved,  specially  by 
the  experiments  of  Moleschott.  He  removed  the  whole 
of  the  liver  from  frogs  ;  and  found  that  in  some  cases 
the  animals  would  live  as  long  as  three  weeks  :  yet  no 
trace  of  bile  acids  could  be  found  in  their  blood,  mus- 
cles, gastric  juice,  lymph,  or  urine. f  Kunde  preceded 
Moleschott  in  observations  with  the  like  object,  but 
they  are  less  valuable  ;  Kunde's  frogs  survived  at  the 
most  the  fourth  day.ij:  Johannes  Miiller  is  commonly 
said  also  to  have  extirpated  the  livers  of  frogs  ;  but,  as 
his  experiments  are  related  by  Kunde,  he  seems  only  to 
have  thrown  a  ligature  around  the  vessels  of  the  liver, 
and  afterwards  to  have  found  the  same  changes  with 
nitric  acid  in  the  blood  of  healthy  frogs  as  in  the  blood 
of  those  operated  upon.  || 

It  may  be  objected  to  Moleschott's  and  Kunde's  ex- 
periments, that  they  used  chemical  tests,  not  now  very 
greatly  trusted;  for  it  is  known  that,  in  complex  organic 
fluids  like  blood  and  urine,  Pettenkofer's  test  may  not 
at  once  detect  the  presence  of  bile  acids.  And  a  still 
further  objection  may  be  made  ;  for  when  Leyden  tied 
the  bile  duct  only  of  frogs,  no  jaundice  was  seen  at  the 
end  of  8  or  14  days.  No  trace  of  bile  was  found  in  the 
blood  ;  and  even  in  the  liver  not  the  least  appearance 
of  jaundice  was  seen.§  If  no  jaundice  be  caused  by 
tying  the  duct,  can  any  be  looked  for  after  removing  the 
liver  ?     The  vital  processes  in  these  animals  are   very 

*  Liebermeister,  Bciti'dge  zur  path.  Aunt,  iind  Kliiuk  d.  Leberkrankheiten,  Tub- 
ingen, 1864,  p.  241. 
•  t  Moleschott,  Arch.f.phys.  Heilkundc,  1852,  p.  479. 
X  F.  T.  Kunde,  De  hepatis  ranarum  exstirpatione,  Diss.  Inaug.  Berolin.  1850. 
II  Johannes  Miiller,  quoted  by  Kunde,  op.  cit.  p.  6. 
§  Leyden,  Beitrdge  zur  Path,  des  Icterus,  Berlin,  1866,  p.  19. 

G2 


84  Place  of  the  Secretion  of  Bile. 

slow ;  and  warm  blooded  animals  do  not  survive  the 
severe  injuries  inflicted  by  the  removal  of  the  liver. 

Schmulewitsch,  again,  in  Ludwig's  laboratory,  made 
some  observations  which  seemed  to  show  that  the  bile 
is  really  formed  from  the  blood  by  the  liver.  He  passed 
dog's  blood  whipped,  and  diluted  with  saline  solution, 
through  the  portal  vein  of  a  recently-killed  rabbit,  and 
found  that  the  secretion  of  bile  went  on,  in  a  less 
degree  than  in  health,  for  two  hours  and  more,  after 
death.*  Pfliiger,  however,  passed  a  3  per  cent,  saline 
solution  through  the  liver  of  a  recently-drowned  cat  in 
whom  the  rigor  mortis  was  just  beginning  to  shew  itself; 
he  found  an  abundant  secretion  of  a  dilute  bile  to  take 
place,  and  to  last  for  more  than  an  hour.  This  will  show 
that  the  supposed  secretion  of  the  bile  was  only  a 
transudation  of  serum  into  the  fine  biliary  passages,  and 
a  pushing  of  the  bile  secreted  before  death  into  the 
large  biliary  ducts,  giving  rise  to  the  factitious  appear- 
ance of  secretion.! 

Rohrig  has  repeated  both  Schmulewitsch's  and  Pflii- 
ger's  experiments,  and  decides  in  favour  of  the  former. 
He  finds  that  no  bile  makes  its  appearance  when  only 
saline  solution  is  thrown  into  the  liver  ;  whereas  abun- 
dance appears  when  the  animal's  own  whipped  blood 
is  again  and  again  passed  through  it.  J 

In  this  state  of  affairs,  where  every  experiment,  which 
tends  to  shew  that  the  liver  itself  secretes  the  bile,  not 
merely  separates  it,  is  met  with  another  to  show  that 
the  first  experiment  does  not  answer  its  purpose,  we 
shall  be  compelled  to  fall  back  on  the  general  principles 
of  physiology. 

*  Schmulewitsch,  Arbcitcn  aiis  dcr  phys.  Anstalt  zu  Leipzig,  1868,  p.  113.  M. 
Schiff  says  that  in  1862  he  made  a  similar  experiment  to  that  of  Schmulewitsch  ; 
and  after  passing  blood  through  the  liver  for  a  quarter  of  an  hour  about  17  centi- 
grammes of  freshly-secreted  bile  were  collected  (Schivclz.  Zc.itschrift  f.  Med. 
1862.  Bd  I.  p.  50.  quoted  in  Arch.  f.  ges  Phys.  1870,  Bd.  iii.  p.  Cio.) 

f  Pfliiger,  Arch.f.  d.  ges.  Phys.  1871.  Bd.  iv.  p.  54. 

l  Rohrig,  Strieker's  Med.  Jahrbb.  Wien,  1873.  p.  2  ^y 


Place  of  the  Secretion  of  Bile.  85 

Looking  then  at  the  constituents  of  the  bile  :  it  will 
be  seen  that  the  bile  acids  and  the  bile  pigment  are  the 
only  two  which  are  peculiar  to  it.  The  cholestearin, 
lecithin,  fats,  and  inorganic  salts  are  found  in  abundance 
in  other  parts  of  the  body.  The  bile  pigments  and  bile 
acids  are  however  only  found  in  the  liver  and  bile  ;  * 
they  cannot  be  found  in  the  blood  in  health,  even  in  that 
of  the  portal  vein, f  as  the  cholestearin,  lecithin,  and  fats 
are.  From  whence  it  is  inferred  that  the  pigments  and 
bile  acids  are  formed  in  the  liver.  J  To  this  it  may  be  ob- 
jected that  the  facts  are  not  good.  The  failure  of  physio- 
logical chemistry  to  detect  bodies  in  no  way  warrants  the 
assertion  of  their  absence  in  a  fluid.  Of  late  years, 
even  physiological  chemists  have  succeeded  in  detecting 
both  pigments  and  acids  in  the  urine  in  health,  a  sure 
sign  that  they  must  be  present  in  the  blood,  as  it  would 
not  be  assumed  that  the  kidneys  were  able  to  secrete 
them.  To  this  it  may  be  said  that  in  healthy  urine  the 
pigments  and  acids  are  present  in  very  minute  quantity 
and  that  this  minute  quantity  probably  corresponds  to 
the  amount  which  escapes  re-excretion  by  the  liver 
when  the  pigments  and  acids  are  taken  up  by  the 
mesenteric  veins  and  lacteals  ;  that  the  bile  pigments 
and  acids  have  been  detected  in  the  blood  in  cases  of 
jaundice,  so  that  if  they  existed  in  any   quantity  in  the 

*  Cloez  and  Vulpian  {Coinptes  rendus,  1857,  t.  xlv.  p.  340)  say  that  they  have 
found  taurocholic  acid  in  the  supra-renal  bodies  of  herbivorous  animals.  They  did 
not,  however,  obtain  any  crystalline  body,  but  only  a  sulphur-containing  body,  nor 
did  they  even  use  Pettenkofer's  test,  or  make  an  elementary  analysis.  I  should 
hesitate  in  drawing  any  conclusions  from  their  work. 

f  C.  G.  Lehmann  could  find  none  of  the  bodies  peculiar  to  the  bile  in  the  blood 
of  the  portal  vein  of  the  hox5&  {yournal  de  Pharmacie  et  de  chemie,  1852,  t.  xxi. 
p.  396)  nor  Hoppe-Seyler  in  the  portal  blood  or  chyle  of  5  dogs  {Arch.  f.  path, 
Anat.  1863,  Bd.  xxvj.  p.  536.) 

J  It  may  be  noted  that  Drosdoff  [Zeitschriftf.  phys.  Chemie,  1877,  Bd.  j.  p.  233.) 
has  found  the  cholestearin  and  lecithin  in  four  or  five  times  as  great  quantity 
in  the  hepatic  as  in  the  portal  vein.  Beneke  believes  that  cholestearin  and 
lecithin  are  formed  in  the  liver,  and  absorbed  by  the  intestines  into  the  blood ;  and 
that  the  liver  is  the  source  in  the  ceconomy  of  these  bodies.  {Gi' and  lime  11  der 
Pathologic  dcs  Stoffwechscls,  Berlin,  1874,  p.  194.) 


86  Place  of  the  Secretion  of  Bile. 

blood  in  health,  equal  say  to  the  cholestearin,  it  would 
be  impossible  that  they  could  escape  detection.  I  think 
myself  this  reasoning  is  valid;  for  the  case  of  the  urine  of 
jaundice  in  which  for  so  long  the  bile  acids  lay  undetected 
is  not  in  point,  as  the  bile  acids  could  not  be  found  at 
any  time,  while  it  is  acknowledged  that  they  can  be 
found  in  the  blood  in  cases  of  jaundice  or  artificial 
injection. 

But  there  is  yet  another  argument.  It  is  said  that 
the  liver  is  able  to  draw  to  itself  and  forthwith  ex- 
crete whatever  bile  pigments  may  be  present  in  the 
blood.  Schiff  found,  when  bile  is  injected  into  the 
duodenal  fistula  of  an  animal,  which  has  also  a  biliary 
fistula,  that  a  great  increase  of  the  secretion  of  bile 
from  the  biliary  fistula  takes  place  in  12  or  15  minutes 
after  the  injection.  And  with  animals  in  whom  an 
amphibolous  biliary  fistula  had  been  made,  that  is,  a 
fistula  in  which  the  bile  could  be  directed  into  the 
intestine,  or  to  the  outside  of  the  body  at  pleasure,  it 
was  found  that  a  much  greater  amount  of  bile  was 
secreted  after  the  bile  was  allowed  to  pass  into  the  gut 
than  after  it  had  been  led  out  of  the  body.  Further,  if 
the  bile  acids  were  injected  into  the  veins,  stomach,  or 
duodenum,  or  under  the  skin,  a  great  increase  in  the 
solids  of  the  bile  took  place.*  Prince  Tarchanoff  found 
that  when  haemoglobin  or  bilirubin  was  injected  into 
the  veins  of  an  animal  with  a  permanent  fistula,  a 
great  increase  in  the  amount  of  pigment  took  place. f 
Huppert,  however,  found  that  when  the.  bile  acids  are 
injected  into  the  veins  of  an  animal  with  a  biliary 
fistula,  only  a  fourth  or  a  third  appeared  in  the  bile,  J 
and  Socoloff  has  repeated  these  experiments  with  the 
bile  acids,  and  thinks  the  liver  has  little  power  of  ex- 

*  Schiff,  Arch.f.  d.  gesaiiimtc  Physiologie,  1870.  Bd.  iii.  p.  598. 

f  Tarchanoff,  ibid,  1874,  Bd  ix.  p.  329. 

J  Huppert,  Arch.  d.  Hcilknnde,  1864,  p.  244. 


Source  of  the  Pigments.  87 

creting  them.*  Rohrig  also  found  that  when  a  solution 
of  glycocholate  of  soda  is  injected  into  the  portal  vein, 
the  pulse  becomes  slow,  just  as  if  the  salt  had  been 
injected  into  a  systemic  vein  :"f  an  appearance  which 
would  hardly  be  consistent  with  the  view  that  the  liver 
has  great  power  of  rapidly  excreting  the  bile  acids. 

By  these  observations  the  conjecture  of  some  phy- 
sicians, such  as  Dr.  George  Budd,:|:  Skoda, §  and  Dr. 
George  Harley,||  that  the  bile  pigments  are  formed  in  the 
blood,  not  in  the  liver ;  and  that  the  bile  acids  only  are 
formed  in  the  liver,  may  be  thought  to  be  favoured.  It 
is  of  course  possible  that  the  hepatic  cells  may,  as  Dr. 
Michael  Foster  says, 51  avail  themselves  of  certain  half- 
made  materials,  such  as  haemoglobin,  the  transference 
of  which  into  pigment  would  be  easy  in  the  opinion 
of  many  physiological  chernists.  From  Schiff's  and 
Tarchanoff's  experiments  it  is  argued  that  the  liver  so 
rapidly  excretes  the  bile  pigments,  that  it  at  once 
gets  rid  of  all  contained  in  the  blood  or  which 
are  formed  there;  so  that  in  health  no  bile-pigment 
can  be  detected  in  the  blood.  I  must  own  that  these 
excretions  must  be  rapid  indeed:  more  rapid  than  any 
other  excretion  that  is  known. 

What  vessel  furnishes  the  elements  of  the  bile?  It  has 
been  much  disputed  whether  the  portal  vein  or  the 
hepatic  artery  supply  to  the  liver  the  materials  out 
of  which  the  bile  is  formed.  The  strife,  which  Dr. 
Michael  Foster  thinks  is  over  a  barren  problem,**  has 
been  prolonged  by  the  observations  and  experiments 
which    are   brought  forward,    and  which  tend  to  show, 

*  Socoloff,  Arch.  f.  d.  ges.  Phys.  1875,  Bd.  xi.  p.  166. 

t  Rohrig,  Arch.  d.  Heilkunde,  1863,  p.  412. 

I  Budd,  On  Diseases  of  the  Liver,  Lond.  1857,  P-  467* 
§  Skoda,  Deutsche  Klinik,  1859,  p.  286. 

II  George  Harley,  Jaundice,  Lond.  1863,  p.  ir. 

%  Michael  Foster,  Text-book  of  Physiology,  London,  1S77,  p.  191. 
**  Michael  Foster,  loc.  cit. 


88  Ligature  of  the  Portal  Vein. 

on  the  one  side,  that  the  hlood  of  the  portal  vein  is 
not  necessary  to  the  secretion  of  bile,  and  on  the  other, 
that  it  is. 

These  experiments  go  back  as  far  as  the  days  of 
Malpighi,  who  speaks  of  ligature  of  the  hepatic  artery 
close  to  the  cceliac  trunk  as  an  often-repeated  experi- 
ment :  after  the  ligature  a  large  amount  of  dilute  bile 
was  secreted.* 

Abernethy  noted  in  a  well-nourished  child,  of  about 
ID  months,  brought  to  St.  Bartholomew's  Hospital  for 
dissection,  that  the  portal  vein  terminated  in  the  vena 
cava  inferior,  nearly  on  a  line  with  the  renal  veins.  The 
gall-bladder  contained  a  teaspoonful  of  bile,  bitter  to 
the  taste,  which  became  green  when  dilute  nitrous  acid 
was  added. t  Abernethy  was  evidently  inclined  to  the 
belief  that  the  blood  of  the  portal  vein  was  not  neces- 
sary for  the  formation  of  bile. 

Under  the  two  heads  of  obstruction  of  the  portal  vein 
and  obstruction  of  the  hepatic  artery,  the  different  ob- 
servations and  experiments  may  be  arranged. 

i.  Obstruction  of  the  portal  vein.  When  the  portal 
vein  of  a  mammal  is  suddenly  tied,  the  animal  dies 
within  24  hours  at  least  of  the  operation  :  the  greater 
number  die  immediately.  In  four  rabbits  who  survived 
the  operation  about  24  hours,  Moos  found  an  absence 
of  bile  and   sugar   in  the    liver.       In    frogs,    who    live 

*  Malpighi,  Opera,  London,  t685.  De  Liene,  p.  120  in  the  Dc  visccrum  Stnic- 
ttira.  Benjamin  Phillips  says  that  he  tied  both  portal  vein  and  hepatic  artery,  but 
noticed  only  a  decrease  of  the  secretion  of  bile.  {Land.  Med.  Gaz.  1833,  vol.  xii. 
p.  423.)  Simon  of  Metz  is  said  to  have  done  the  same,  (jfoiirnal  de  Progres, 
1828,  t.  vii.  p.  215.)     I  have  not  verified  this  last  statement. 

f  Abernethy,  Phil.  Trans.  1793,  Part  i.  p.  61.  It  is  just  mentioned  by  Lawrence 
(Med.  Chir.  Trans.  1814,  Vol.  v.  p.  174)  that  a  teacher  of  anatomy  in  London  had 
met  with  a  like  state  in  the  body  of  a  much  older  person.  Benjamin  Phillips 
{Land.  Med.  Gaz.  1833,  Vol.  xij.  p.  423)  gives  two  other  cases;  one  by  Lieutaud, 
(Historia  Anat.-Med.  Paris,  1767,  t.  j.  p.  190)  but  this  is  a  case  of  absence  of  the 
liver  and  spleen  ;  and  another  by  J.  J.  Huber,  {Observ.  aliqii.  Anat.  Casselis,  1760, 
p.  34)  in  which  the  portal  vein  is  said  to  have  passed  through  the  diaphragm, 
e  ramis  siiis  hepaticis  niox  productus,  but  nothing  is  said  of  the  bile. 


Ore's  Method.  89 

much  longer,  he  found  the  secretion  decreased  dur- 
ing the  first  few  days  after  the  operation  ;  while  if  the 
animal  lived  long,  say  four  weeks,  the  bile  was  ap- 
parently increased  in  amount.*  Ore  discovered  a  plan 
by  means  of  which  a  gradual  obliteration  of  the  portal  vein 
took  place.  In  all  his  dogs  he  found  the  gall-bladder  full 
of  bile.t  It  would,  however,  have  been  more  conclu- 
sive, .as  Bernard  remarks,  if  a  biliary  fistula  had  been 
established  at  the  same  time  that  the  portal  vein  was 
tied,J  as  the  gall-bladder  may  have  been  filled  by  bile 
secreted  before  the  operation.  In  disease  it  is  not  very 
uncommon  to  find  a  complete  obliteration  of  the  portal 
vein  by  clots,  and  in  these  cases  the  gall-bladder  is 
often  full.  This  of  course  affords  as  much  or  as  little 
proof  as  Ore's  experiments. 

Schiff,  in  some  of  his  expeririients  on  the  influence  of 
the  circulation  in  the  liver  on  the  secretion  of  bile,  tied 
all  the  structures  in  the  hepato-duodenal  ligament,  save 
the  hepatic  artery.  Occasionally,  however,  he  tied  the 
vessels  separately;  the  bile  was  received  by  means 
of  a  cannula  tied  in  the  common  duct.  In  cats, 
the  ligature  was  followed  by  death  in  40  to  go  minutes, 
no  bile  being  secreted.  The  creatures  rapidly  be- 
came torpid,  and  artificial  warmth  in  no  way  less- 
ened this  state.  No  rabbit  survived  the  operation 
longer  than  54  minutes.  According  to  Schiff,  the 
cause  of  death  seemed  to  be  the  accumulation  in  the 
in  the  blood  of  the  materials  which  ought  to  be  excreted 
by  the  bile. 

In  dogs  and  cats,  Schiff  tied  the  portal  vein  after  Ore's 
method,  somewhat  modified.    In  these  creatures  he  found 

*  Moos,  Uutersuchiingen  u.  Bcobachtuiigcn  uebcr  den  Einjluss  d.  Pfortadcrcnt- 
zundung  auf  die  Bildung  der  Galle  und  des  Ztickers  in  der  Leber,  Leipzio-  and 
Heidelberg,  1859.  pp.  17  and  24. 

t  Ore,  Comptes  rendus,  1856,  t.  xliii.  p.  463. 

t  Claude  Bernard,  Lemons  siir  les  pvoprietes,  &c.  des  Uquides  dc  Porganismc, 
Paris,  1859,  t.  ij.  p.  195. 


go  Schiff's  Experiments. 

that  the  portal  vein  above  the  place  of  ligature  made 
anastomoses  for  itself  with  the  general  systemic  veins  : 
in  cats  especially  it  was  seen  that  a  large  branch  from  the 
umbilicus  passed  by  the  side  of  the  liganientum  teres  of 
the  liver  into  the  portal  vein.  To  this  vein  Schiff  gives  the 
name  of  vena  parumbiUcalis.  These  observations  do  not, 
in  Schiff's  opinion,  contradict  the  general  belief  that  the 
bile  is  made  by  the  portal  blood.  He  made  also  an 
attempt  to  turn  the  blood  from  the  renal  artery  into  the 
portal  vein,  but  the  experiments  did  not  succeed  on 
account  of  the  clotting  of  the  blood  in  the  vessels. 
The  experiments  on  three  animals  lasted  but  a  quarter 
of  an  hour,  during  which  time  the  liver  showed  a  dark 
red  colour,  but  the  secretion  of  bile  went  on,* 

In  another  set  of  experiments,  Schiff  intended  to 
throw  light  on  the  absorption  of  bile  by  the  portal 
system  ;  he  found  that  the  amount  of  bile  passed  out  of 
a  biliary  fistula  in  a  dog  whose  portal  vein  was  tied, 
after  the  injection  of  bile  into  the  intestines,  was  no  less 
than  in  one  whose  portal  vein  was  free,  so  that  the  bile 
was  absorbed  from  the  intestines,  carried  into  the  gene- 
ral circulation  and  yet  was  at  once  discharged  by  the 
liver.  It  is  a  pity,  however,  that  Schiff  did  not  ascer- 
tain that  no  immediate  communication  in  this  dog 
between  the  intestinal  vessels  and  the  upper  part  of 
the  portal  vein  had  been  set  up.t 

Rohrig  found  that  if  the  vessels  in  the  hepato-duo- 
denal  ligament  were  firmly  compressed,  the  biliary  se- 
cretion was  at  once  arrested.  If  the  compression  did  not 
last  more  than  a  few  minutes,  the  liver  slowly  recovered 
itself.  If  it  lasted  longer,  the  animals  died  without  another 
drop  of  bile  being  secreted.  If  the  portal  vein  alone 
were  compressed,  there  was  a  considerable  decrease  of 


*  Schiff,  CanstatV s  yahrcsbcricht /.  1862,  Bd.  i.  p.  127. 
f  Schiff,  Arch./,  d.  ges.  Phys.  1870,  Bd.  iii.  p.  608. 


Ligature  of  the  hepatic  artery.  gi 

the  secretion  of  bile,  but  no  such  complete  cessation,  as 
there  was  after  pressure  on  both  vessels.  * 

ii.  Ligature  of  the  hepatic  artery.  It  has  been  already 
said  that  Malpighi  noted  a  flow  of  dilute  bile  after  liga- 
ture of  the  hepatic  artery,  Brachet  and  Fouilhoux  say 
that  they  attempted  to  tie  the  portal  vein  or  the 
hepatic  artery  in  living  animals.  The  ligature  of  the 
artery  appeared  to  them  to  suspend  the  secretion  of  bile, 
but  not  the  ligature  of  the  portal  vein.  They  are  cau- 
tious enough,  however,  to  add  that  they  draw  no  con- 
clusions from  these  appearances,  as  the  animals  did  not 
live  long  enough. f 

KottmeierJ  and  Kuthe§  found  that  no  bile  was  se- 
creted after  ligature  of  the  hepatic  artery  of  rabbits,  while 
Rohrig  found  but  a  slight  decrease  in  the  amount  of 
bile  secreted  after  the  ligature  of  the  hepatic  artery  ;||  in 
what  animal  does  not  appear. 

Schiff  found  that  the  ligature  of  the  hepatic  artery, 
behind  the  stomach  of  a  large  dog,  was  no  hindrance  to 
the  secretion  of  bile.  In  fact  the  vessel  never  became 
empty  of  blood.  He  found  in  many  dogs,  that  the 
ligature  of  the  hepatic  artery  neither  caused  a  stoppage 
of  the  arterial  supply. of  blood  to  the  liver  nor  of  the  secre- 
tion of  bile.  In  both  dogs  and  cats  there  are  branches  to 
the  liver  from  the  phrenic  arteries,  from  the  left  coronary 
arteries  of  the  stomach  and  from  a  small  branch  accom- 
panying the  bile  ducts  :    so  that  it  is  necessary,   to  cut 

*  Rohrig,  Strieker's  Med.  yahrhb.  1873,  p.  242. 

t  Brachet  and  Fouilhoux,  quoted  by  Raikem,  Observations,  etc.  sur  quelques 
affections  morbides  de  la  veine  porte,  in  the  Memoires  de  V Academic  royale  de  Medc- 
cine  de  Belgiqne,  1849,  p.  15. 

J  Kottmeier,  Zur  Kenntniss  dey  Leber,  Diss.  Inaug.  Wiirzburg,  1857,  P-  '^^■ 
Some  experiments  were  made  on  frogs.  In  rabbits  the  gall  bladder  was  found 
empty,  and  no  bile  in  the  intestines.  See  Cohnheim  and  Litten's  observations 
on  the  next  page. 

§  Kiithe,  Studien  des  phys.  Instituts  zii  Amsterdam,  herausgegeben  von  Heynsi-us, 
Leipzig  and  Heidelberg,  1861,  p.  35.  No  glycogen  or  sugar  was  found  in  the 
liver  of  rabbits. 

II  Rohrig,  loc.  cit. 


g2  Ligature  of  the  hepatic  artery. 

off  all  supply  of  arterial  blood  from  the  liver,  that  the 
three  branches  of  the  coeliac  trunk  and  the  phrenic 
arteries  should  be  tied.*  In  case  of  ligature  of  the 
portal  vein  Schiff  noticed  no  enlargement  of  the  hepatic 
artery.  Cohnheim  and  Litten  confirm  the  statement 
that  the  arterial  blood  cannot  be  cut  off  from  the  liver 
by  ligature  of  the  hepatic  artery  in  dogs.  They  find, 
however,  that  in  rabbits  this  operation  is  possible,  but 
is  rapidly  followed  by  death  within  the  first  20  hours. 
A  change  in  the  liver  takes  place  which  Cohnheim  and 
Litten  call  necrosis.  On  section  the  liver  is  seen  to  be 
soft,  the  colour  grey  3'ellow,  not  a  trace  of  polish  on  the 
surface,  the  acini  invisible  :  under  the  microscope  the 
the  section  is  seen  clouded  and  indistinct,  and  in  some 
cases  the  nuclei  not  discernible  with  the  help  of  log- 
wood.f  These  observations  show  the  important 
influence  which  the  hepatic  artery  has  upon  the  nutrition 
of  the  liver;  but  they  are  not  much  aid  in  determining  the 
question  if  arterial  or  portal  venous  blood  be  essential 
to  the  secretion  of  bile. 

Obstruction  of  the  hepatic  artery  in  disease  is  a 
rare  phsenomenon,  much  rarer  than  portal  obstruc- 
tion. Ledieu  has  recorded  a  case  of  aneurysm  of  the 
hepatic  artery  in  which  that  vessel  was  obstructed,  and 
yet  the  gall-bladder  was  full  of  bile. J  As  the  observa- 
tions of  Schiff  teach,  it  is  very  hard  to  keep  arterial 
blood  out  of  the  liver ;  in  Ledieu's  case  the  pyloric 
artery  was  pervious ;  and  as  this  artery  inosculates 
freely  with  the  coronary  artery  of  the  stomach,  there 
is  no  proof  that  the  liver  was  deprived  of  arterial  blood. 

Reviewing  these  various  observations,  it  will  be  at 
once  seen  that  any  deduction  from  supposed  obstruc- 
tions of  the  hepatic  artery  in  man  is  of  no  value,  and  the 

•  Schifif,  Canstatt's  Jahrcsbcricht  f.  1862,  Bd.  i.  p.  126. 
f  Cohnheim  and  Litten,  Arch./,  palli.  Aiuit.  1876,  Bd.  Ixvii.  p.  162. 
+  Ledieu,  jfonrnal  de  Bjrdcaiix,  1856,  Mars,  reported  in  Schmidt's  Jahrbb.  1857, 
Bd   xciii.  p.  56. 


Review  of  Observations.  93 

whole  of  these  may  be  passed  by  in  silence.  Whether 
the  same  objection  will  apply  to  obstruction  of  the 
portal  vein,  that  is  to  say,  whether  the  portal  or  other 
blood  again  finds  its  way  to  the  liver  in  all  cases,  is  not 
so  certain.  That  the  portal  blood  in  many  cases  does 
not  enter  the  liver,  but  the  general  circulation,  would 
seem  to  be  shown  by  Bernard's  observation  ;  the  blood 
of  the  portal  vein  was  found  anastomosing  with  the  renal 
vein,  and  the  vena  cava  inferior,  thus  reproducing  in 
mammals  the  venous  system  of  Jacobson.*  Other  an- 
astomoses have  been  described  with  the  intestinal  and 
external  systems. 

The  earlier  observations  of  the  passage  of  the  portal 
vein  direct  into  the  vena  cava  cannot  be  made  of  any 
service,  as  the  sources  of  blood  to  the  liver,  other  than 
the  portal  vein,  are  not  spoken  of. 

The  cases  of  sudden  ligature  of  the  portal  vein  which 
Moos  records,  would  doubtless  be  set  aside  by  many 
physiologists  :  yet  it  is  noteworthy  that  24  hours  after 
the  ligature  no  bile  or  sugar  could  be  found  in  the  liver; 
an  effect  hardly  to  be  sought  in  the  operation  itself.  It 
may  therefore  be  thought  that  the  sudden  removal  of 
the  portal  blood,  the  hepatic  artery  being  free,  has  some 
influence  both  on  the  bile  and  sugar-forming  functions 
of  the  liver,  and  that  the  functions  of  the  liver  only  con- 
tinue to  be  properly  performed  when  the  blood  brought 
by  both  sets  of  vessels  reaches  the  lobules.  The  matter 
is,  however,  a  very  difficult  problem  ;  and  I  would  pre- 
fer, with  Bichat,t  to  leave  it  to  the  decision  of  further 
researches. 

*  Bernard,  op.  c'lt.  pp.  igo  and  195.  He  indeed  tied  the  portal  vein  suddenly  on 
a  pigeon :  yet  the  animal  died  the  next  day,  in  spite  of  the  communications  be- 
tween the  portal  and  inferior  cava  in  these  creatures. 

f  Bichat,  Anatomic  generate,  Paris,  1801,  t.  ij.  p.  458.  It  seems  to  have  been 
the  general  belief  in  Bichat's  time  that  the  bile  was  secreted  from  the  portal  vein. 
He  gives  fully  the  reasons  then  prevalent  for  this  belief.  Some  of  them  seem  to 
us  foolish  enough,  and  he  has  an  easy  task  to  refute  them.  Cf.  Haller,  Elcm.  Phys. 
Lugd.  Batav.  1764,  t.  vj.  p.  597,  and  Tiedemann  and  Gmelin,  Rechcrches,  etc.  sur 
la  Digestion,  Paris,  1827,  Partie  ii.  p.  57. 


CHAPTER   VI. 

The  Amount  of  Bile  secreted  in  health    and    the 
Agents  which  affect  it. 

Amount  of  bile  daily  secreted  in  health. — Before  the  ob- 
servation of  biliary  fistulae  in  men  or  animals,  it  was 
impossible  to  do  more  than  guess  at  the  amount  of  bile 
secreted  by  the  liver.  Nevertheless  Haller  set  down 
the  amount  of  bile  daily  secreted  as  24  ounces  ;*  a 
figure  which  approaches  some  of  the  calculations  made 
of  late  years.  Other  physiologists  about  the  same  time 
set  the  amount  much  lower ;  a  few  drachms,  or  an 
ounce  or  two.f 

Later  on,  more  extravagant  views  prevailed  ;  the 
amount  of  bile  secreted  in  the  24  hours  was  calcu- 
lated from  the  quantity  thought  necessary  to  neutralise 
the  acid  chyme,  and  an  ox  was  said  to  secrete  the 
enormous  quantity  of  thirty  seven  and  a  half  pounds 
of  bile  in  a  day.J  Liebig  adopted  this  statement  as  it 
coincided  with  some  of  his  views  on  the  sources  of  the 
bile  and  its  importance  in  the  processes  of  respiration 
and  of  animal  heat:§  indeed  the  estimation  seems  for  a 
time  to  have  been  generally  accepted. 

The  views  of  these  writers  are  indeed  entirely  spe- 
culative ;  and  are  in  no  way  founded  on  observation. 
According  to  Bidder  and  Schmidt,  ||  Douglas,  an  Ameri- 

•  Haller,  Eleiii.  Phys.  Lugd.  Bat.  1764,  t.  vi.  p.  606. 

f  Bianchi,  Historia  Hcpatica,  Genevae,  1725,  t.  i.  p.  116. 

\  C.  H.  Schultz,  dc  aliinentonim  coucGctionc,  Berolini,  1834,  P-  ^oS,  42  ct  scqq. 
quoted  by  Bidder  and  Schmidt,  Die  Vcrdauungssaeftc,  Mitau  and  Leipzig,  1852, 
p.  117. 

§  Liebig,  Animal  Chemistry,  Lond.  1842,  Gregory's  translation,  p.  64. 

II  Bidder  and  Schmidt,  loc.  cit.  They  quote  from  Tiedemann,  Physiologic  dcr 
Vcrdauung,  Ulm,  1835,  p.  268.  The  reference  to  Douglas'  work  is:  Medical 
Repository  by  Mitchill,  New  York,  181 7.  I  have  not  been  able  to  see  a  volume 
of  the  New  York  Medical  Repository  for  1817. 


Biliary  Fistula.       '  95 

can  physician,  was  the  first  in  this  century  to  form  any 
opinion  based  on  the  analogy  of  experiments  on  ani- 
mals ;  and  from  these  data  he  calculated  that  a  healthy 
man  excreted  during  the  24  hours  29  ounces  of  bile. 

Magendie  says  that  in  dogs  the  escape  of  bile  and 
pancreatic  juice  takes  place  by  intervals  ;  about  twice 
in  a  minute  a  drop  of  bile  is  seen  to  rise  from  the 
papilla,  and  this  drop  spreads  itself  uniformly  over  the 
parts  around."'  With  these  two  observers  physiology 
seems  to  have  contented  herself  during  the  first  half  of 
this  century. 

When  Schwann,  therefore,  invented  his  mode  of 
making  bihary  fistulse  in  animals, t  there  appeared 
good  hope  that  the  great  darkness  which  shrouded  all 
that  pertained  to  the  secretion  of  the  bile  might  be 
chased  away.  An  increase  in  knowledge  has  certainly 
taken  place,  but  the  new  method  of  observation  has 
hardly,  done  all  that  might  have  been  looked  for  from 
it  at  the  first  moment  of  its  discovery.  One  important 
defect  is  that  the  bile  is  diverted  from  the  intestine,  out 
of  the  body  entirely  :  a  circumstance  not  without  consi- 
derable infl.uence  upon  the  physiology  of  the  secretion.  J 

Before  considering  the  information  given  by  experi- 
ments, it  will  be  well  to  consider  the  results  of  the 
observations  made  in  man  when  disease  or  accident 
has  formed  a  biliary  fistula.  There  are  very  few  in 
which  any  observations  have  been  made,  and  still 
•fewer  in  which  accurate  and  careful  investigations 
have  been  carried  out :  and  the  observations  are  open 
to  all  the  objections  made  against  biliary  fistulas  in 
animals.  Further,  it  may  be  said  that  the  observations 
are   altogether  untrustworthy,  and  that  they  were  made 


*  Magendie,  Precis  elem.  de  phys,  Paris,  1836,  4e.  ed.  t.  ii.  p.  14. 
f  Th.  Schwann,  Arch.f.  Anat.  Phys.  u.  s.  w.  1844,  p.  127. 

%  I  must  refer  to  special  physiological  works  for  the  method  of  setting  up  a 
biliary  fistula  in  animals. 


g6  Amount  of  Bile  Secreted  in  Man. 

on  persons,  "all  of  whom  were  weakened  by  long  ill- 
nesses, and  most  of  them  by  a  suppuration  ;  and  that  the 
results  in  no  way  represent  the  qualities  of  the  secre- 
tion in  health.  Of  course  these  objections  must  be 
weighed  ;  but  the  results  on  man,  even  if  exhausted  by 
disease,  should  be  compared  with  those  attained  by 
observation  on  healthy  animals,  as  these  are  the  only 
two  paths  of  attaining  knowledge  open  to  us. 

Westphalen's  observations,  already  spoken  of  in  the 
fourth  chapter  of  this  work,  are  those  which  have  been 
made  with  the  greatest  care.*  He  collected  the  bile 
passed  during  every  four  hours  of  the  day  and  night. 
The  flow  showed  very  little  variation,  saving  that 
collected  from  2  to  6  in  the  morning,  which  was 
always  small.  The  other  amounts,  collected  during 
the  day,  varied  from  94*3  and  83*2  grm.  in  the  four 
hours,  while  the  bile  collected  in  night  and  early  morn- 
ing was  on  an  average  only  61  "8  grm.  though  it  was  the 
richest  in  solid  constituents.  Of  these  it  held  2*499 /^r 
cejit.  while  the  bile  secreted  during  the  day  was  but  a 
little. over  2  per  cent. 

The  highest  quantity,  secreted  in  four  hours,  seen 
by  Westphalen  was  125*2  grm.  :  the  lowest  52*2  grm. 
The  average  about  83*9.  Von  Wittich  in  his  case  found 
the  quantity  secreted  in  four  hours  to  be  88  CCf  The 
results  of  the  two  observers  thus  nearly  agree. 

The  quantity  secreted  every  twenty-four  hours  in 
Westphalen's  case  was  on  an  average  of  10  days 
498*85  grm.  The  highest  quantity  noted  was  566*7 
grm.  The  lowest  453*1  grm.  Von  Wittich  estimates 
the  amount  in  his  case  to  be  532*8  C.C.  Johannes 
Ranke  gives  636  C.C.  as  the  average  of  five  observa- 
tions in  his  case. J     These  figures,  however,  are  arrived 


'  II.  Westphalen,  Dcitlsches  Ai'ch.  f.  klin.  Med.  1873.  Bd.  xi.  p.  588.     Sec  also 
above,  p.  61. 

f  Von  Wittich,  Arch.f.  d.  gcs.  Pliys.  1872,  Bd.  vi.  p.  182. 

J  Johannes  Ranke,  Die  Blutvertheiluiig,  Leipzig,  1871,  p.  144. 


Amount  of  Bile  in  Man.  97 

at  by  allowing  for  the  pulmonary  mucus  brought  up 
with  the  bile.  The  sputa  the  day  after  the  closing  of 
the  fistula  amounted  to  135  C.C.  It  is  clear  that 
Ranke's  figures  cannot  claim  strict  accuracy,  but  only 
an  approximation  to  truth.  The  highest  number  given 
by  Ranke  is  922  C.C.  the  lowest  405  C.C. 

There  are  some  other  cases  also  in  which  the  amount 
of  bile  has  been  estimated,  but  perhaps  not  in  so  careful 
a  manner,  or  with  so  much  technical  knowledge.  In  Dr. 
John  Harley's  case,  a  man  of  29,  the  amount  of  bile 
lost  from  the  fistula  during  a  week  was  from  16  to  20 
fluid  ounces  daily  (440  to  560  C.C.)  associated  ''with 
absence  of  bile  from  the  alimentary  canal"*  which  I 
suppose  may  mean  that  the  faeces  were  free  from  colour. 
This  amount  of  bile  daily  excreted  would  closely  agree 
with  that  given  by  Westphalen,  Johannes  Ranke,  and 
von  Wittich.f  Rouis,  in  a  case  of  communication  with 
the  bronchi  of  an  abscess  in  the  liver,  found  that  900 
grammes  of  a  bilious  fluid  were  brought  up  in  40 
hours. J  This  statement,  however,  is  but  little  worth-; 
nothing  definite  is  said  of  the  state  of  the  stools  or  of 
the  amount  of  pus  or  mucus  present. 

In  the  two  following  cases,  the  amount  of  bile  daily 
secreted  was  about  half  of  what  has  been  given  above. 
Dr.  Robinson  found,  in  a  woman  of  64,  whose  stools  were 
"  destitute  of  bile,"  that  the  amount  daily  discharged 
through  the  fistula  was  about  8  fluid  ounces§  (about 
230  C.C.)     And  in   Krumptmann's  case,  the  faeces  were 


*  John  Harley,  Med.  Chir.  Trans.  1866,  vol.  xlix.  p.  8g. 

f  Von  Wittich,  Arch.f.  d.  ges.  Phys.  1872,  Bd.  vi.  p.  181. 

J  Rouis,  Recherches  sur  Ics  suppiiyations  endemiques  dufoie,  Paris,  i860,  pp.  139 
and  424.  Frerichs,  with  his  habitual  inaccuracy  of  quotation,  says  that  the  goo 
grammes  were  collected  within  24  hours.  (Klinik  d.  Lebevkrankheitcn,  Braunsch- 
weig, 1861,  Bd.  ii.  p.  130.) 

§  Robinson,  Med.  Chir.,  Trans.  1852,  vol.  xxxv.  p.  472.  The  fluid  was  pro- 
nounced to  be  bile  by  Dr.  Bence  Jones. 


H 


g8  A  mount  of  Bile  in  Man. 

grey  white,  yet  the  daily  loss  of  bile  is  said  to  have  been 
only  between  7  or  8  ounces.* 

In  Westphalen's  case,  the  amount  of  solids  was  on 
an  average  2*25  per  cent,  varying  from  3*856  to  1-844. 

The  patient  weighed  68  kilogrammes ;  so  that  one 
kilogramme  secreted  in  24  hours  7-34  grm.  of  bile  with 
•166  solid  matter. 

In  Johannes  Ranke's  case  the  amount  of  dry  bile 
was  found  to  vary  from  2"6g  per  cent,  to  4*01  per  cent. 
figures  much  higher  than  Westphalen's,  whose  mean  is 
2'25  per  cent. 

The  patient  weighed  g4lb.  or  47  kilogrammes;  so  that 
one  kilogramme  secreted  in  24  hours  as  minimum  8"6i 
C.C.  of  bile,  containing  -25  grm.  of  solid  matter;  as 
maximum  ig'62  C.C.  of  bile  with  '8  grm.  of  solids. 

The  mean  would  be  that  one  kilogramme  secreted  14 
grammes  of  fluid  bile  containing  0*44  gramme  of  solids 
in  the  twenty-four  hours. 

In  Dr.  Robinson's  case  the  bile  was  noted  to  flow  more 
copiously  in  the  erect  posture  ;  probably  this  was  due  not 
to  increased  secretion  but  to  a  more  rapid  ejection.  Dr. 
Robinson  also  says  that  the  flow  was  more  rapid  after 
meals.  In  Westphalen's  case,  the  chief  meal  was  given 
in  the  middle  of  the  day.  On  certain  days  the  meal 
was  put  off  for  several  hours,  but  no  change  in  the 
amount  or  concentration  of  the  bile  was  noted.  On 
two  days  abundance  of  drink  was  given  by  the  mouth  ; 
but  no  increased  flow  or  marked  dilution  of  the  bile  fol- 
lowed, while  the  urine  was  doubled  in  amount.  A  dose  of 
calomel  also  was  followed  by  no  increase  in  the  amount 
of  bile.  Quinine,  given  in  doses  of  two  grammes,  (30 
grains)  could  not  be  found  in  the  bile. 

This  is  all  that  I  have  been  able  to  gather  from 
direct   observations  on   man.     Observations   upon   ani- 

•  Krumptmann,  Lund.  Med.  Record,  1873,  p.  264,  quoted  from  li'/t-vur  Ccntral- 
blatt  lor  March,  1873. 


Amount  of  Bile  in  Dogs.  gg 

mals,  many  of  which  have  been  made  with  very  great 
care  and  accuracy,  promise  to  give  far  wider  informa- 
tion. It  must  first  be  said  that  Bouisson  arrived,  by 
methods  which  must  be  thought  quite  inadequate  to  this 
purpose,  at  the  conclusion  that  the  quantity  of  bile  daily 
secreted  was  about  6  ounces  or  ig2  grammes.  He  in- 
jected water  from  the  liver  into  the  intestine  by  the 
hepatic  duct  and  found  that  the  fluid  divided  itself  into 
two  equal  parts;  one  passed  into  the  intestine  ;  the  other 
into  the  gall  bladder  ;  the  amount  in  the  gall  bladder 
was  an  ounce  and  a  half  or  48  grammes.  The  gall 
bladder  empties  itself,  he  says,  twice  a  day  ;  and  thus 
the  amount  of  bile  daily  secreted  would  be  6  ounces  or 
ig2  grammes,  as  stated  above.* 

Blondlot  found  that  the  dog  on  whom  he  had  esta- 
blished a  biliary  fistula  secreted  daily  about  40  to  50 
grammes.  He  calculates  from  this  that  man  would 
secrete  from  200  to  250  grammes  of  bile  daily. f 

Hermann  Nasse,  the  Professor  of  Physiology  in  the 
University  of  Marburg,  made  in  1847  with  the  assistance 
of  Platner,  the  first  attempt  at  any  accurate  estimation 
of  the  amount  of  bile  daily  secreted  by  the  dog.  J  He 
found  large  fluctuations  in  the  same  dog  on  the  same 
diet,  observations  which  have  been  repeated  by  the 
latest  authorities  on  the  same  matter,  the  Edinburgh 
Committee.  Nasse's  work  is  but  little  known  in 
England,  probably  because  it  was  published  under 
the  form  of  an  academical  dissertation,  ad  novi  Prorec- 
toris  inaiLgurationem. 

Bidder  and  Schmidt  made  an  immense  number  of 
experiments  both  on  beasts  and  birds.  Beginning  with 
cats,  they  passed  on  to  dogs,  comparing  their  observa- 

*  Bouisson,  de  la  bile,  Montpellier,  1843,  p.  54. 

f  Blondlot,  Essai  sur  les  fonctions  diifoie,  Paris  and  Nancy,  1846,  pp.  59  and  61. 
X  Herm.  Nasse,   Coiniiwnfatio   de  bills  quotidie  a  cane  secreta  copia  et  indole, 
Marburg,  1851. 

H  2 


100 


Bidder  and  Schmidfs  Estimations. 


tions  on  these  carnivorous  animals  with  experiments  on 
sheep  and  rabbits,  supplemented  by  some  on  the  her- 
bivorous goose  and  the  carnivorous  crow.  They  give 
the  following  table  as  the  mean  of  their  observations.* 


I  Kilogramme  of 

Cat. 

Dog. 

Sheep. 
1-059 

Rabbit. 

Goose. 

Crow. 

• 
In  one  hour 

o-6o8 

0-824 

5-702 

•491 

3'oo4 

Liquid 
bile. 

grammes 

0-034 

0-042 

0-056 

0-103 

0-034 

o-2ig 

Dry 
bile. 

In     twenty-four 
hours    secretes   - 
in  grammes 

14-5 

19-990 

25-416 

136-84 

11-784 

72-096 

Liquid 
bile. 

o-8i6 

0-988 

1-344 

2-47 

0-816 

Dry 
bile. 

This  table  represents  the  mean  of  observations  made 
on  the  following  plan  :  a  biliary  fistula  was  established, 
and  as  soon  as  the  gall-bladder  was  emptied  of  all  its 
bile,  and  the  fresh  secretion  of  the  liver  began  to  run, 
the  whole  of  the  bile  passed  during  every  quarter  of  an 
hour  was  received  in  weighed  glass  bulbs.  At  the  end 
of  three  hours  the  animal  was  killed ;  the  weights  of  the 
body,  liver,  fluid  bile,  and  dry  bile,  were  then  compared. 
The  biliary  fistula  was  made  an  infinite  variety  of  times ; 
so  long  after  a  meal,  or  after  so  much  food  had  been 
given,  and  an  average  struck  of  all  these  observations 
for  the  24  hours,  for  each  kilogramme  of  weight.  An 
estimation  made  on  such. a  method  hardly  recommends 
itself.  As  Claude  Bernard  has  pointed  out,  the  stature 
and  size  of  the  animal  are  left  out  of  consideration. f 
And  the  weight  of  the  entire  body  is  not  at  all  unim- 
portant, for  Heidcnhain,  by  comparing  Bidder  and 
Schmidt's   figures    for  sheep    and    rabbits,   shows   that 

*  Bidder  and  Schmidt,  Die  Vcrdaniiiii^ssacftc,  Mitau  and  Leipzig,  1852,  p.  209. 
f  Claude  Bernard,  Lcroiis  sur  hs  ptu/'riLics  &c.  dcs  liqnidcs  dc  rurgdiiisiiic,  Paris, 
1859,  t.  ii.  p.  205. 


Relation  of  Weight  of  Liver  to  Bile.  loi 

as  the  weight  of  the  whole  body  increases  so  the  amount 
of  bile  for  every  kilogramme  of  body-weight  decreases. 

Guinea  Pig.  Rabbit.  Sheep. 

Mean  weight 518-400       i525-8oo       23377-000 

Mean  amount  of  bile  for  every  |    ^.^^^  ^.^^^  ^.^^^ 

kilogramme  in  one  hour.  J 

Now  the  smaller  the  animal  the  larger  the  liver,  and 
vice  versa.  In  guinea  pigs,  the  ratio  of  weight  of  liver  to 
whole  body  is  i:  27*3;  in  rabbits,  i:  33'5  ;  in  sheep, 
i:  53*57.  But  this  is  not  the  sole  cause;  for  i  kilo- 
gramme of  sheep's  liver  secretes  62'83  grm.  in  the  hour  ; 
of  rabbit's  liver,  169-37  g^"^-  5  o^  guinea  pigs,  185-54 
grm  -.  that  is,  the  liver  of  guinea  pigs  secretes  more, 
weight  for  weight,  than  those  of  either  rabbits  or  sheep. 
And  this  is  more  striking  if  the  following  figures  be 
compared :  there  is  secreted  every  24  hours  by 


Body     .     . 

Liver     . 

If,  however,  the  amount  of  solids  in  the  bile  of  the 
three  animals  be  compared,  altogether  a  different  pro- 
portion is  given.  Of  solid  bile,  each  kilogramme  of 
guinea  pig  secretes  in  the  hour  -ogS  grm.  each  kilo- 
gramme of  liver  2-67  grm.  Of  rabbits,  -103  grm.  ; 
liver,  3-74  grm.  Of  sheep,  -0672  grm  ;  liver,  3-55  grm. 
So  it  is  clear  that  the  great  amount  of  bile  secreted  by 
the  guinea  pig  is  due  solely  to  a  large  amount  of  water. 
If  the  amount  of  fluid  bile  for  each  kilogramme  of  guinea 
pig  and  rabbit  be  compared,  it  is  7-326:  5-070;  while 
the  proportion  of  solid  bile  is  0*002  :  0-103.  ^  more 
than  complete  reversal  of  the  proportion. 

If,  too,  instead  of  a  kilogramme  of  body-weight,  the 
kilogramme  of  liver-weight  be  taken,  the  same  is  ob- 
served.     One  kilogramme   of  rabbit   liver  will   secrete 


Guinea  Pig. 

Rabbit. 

Sheep. 

I 

5-6 

I 

8^ 

37-S     j 

(times       of     own 
>     weight  of  fresh 

4-467 

4-064 

1-507. 

)     bile. 

102  Relation  of  Weight  of  Liver  to  Bile. 

of  fluid  bile  169-37  i"  ^^  hour,  against  185-54  by  guinea 
pig  liver.  Of  solids,  the  rabbit  liver  secretes  3 '74, 
against  2*67  by  the  guinea  pig  liver.  Heidenhain 
thinks  himself  entitled  to  express  the  opinion,  but  not 
as  a  distinct  doctrine,  that  when  the  amount  of  water 
passing  from  the  liver  is  increased,  the  solids  in  the  bile 
are  decreased.* 

A.  Wolf  agrees  with  Heidenhain  as  to  the  relation 
between  the  size  of  the  liver  and  the  amount  of  bile. 
He  thinks  that  animals  which  are  small  and  young,  that 
is,  whose  liver  is  large,  secrete  more  bile  ;  and  that  the 
amount  of  the  secretion  is  in  direct  ratio  to  the  size  of 
the  liver.  He  has  only,  however,  experimented  on  two 
young  dogs.f 

The  views  of  the  Edinburgh  Committee  are  opposed 
to  those  of  Heidenhain  and  Wolf.  They  found 
large  variations  in  dogs  which  they  could  not  explain 
either  from  the  food  or  weight.  They  did  not,  however, 
make  observations  on  the  size  of  the  liver,  but  they  re- 
mark that  it  is  improbable  that  this  circumstance  deter- 
mines the  amount  of  the  biliary  secretion,  the  great 
variation  in  the  same  animal  from  day  to  day  being 
opposed  to  this. J  They  give  a  table  of  the  average 
amount  of  bile  secreted  by  each  kilogramme  of  dog. 
(see  p.  104.) 

Westphalen,  from  his  direct  experiment  on  man, 
found  that  one  kilogramme  produced  7-34  grammes 
of  fluid  bile,  and  o-i66  gramme  of  dry  bile  in  the 
24  hours. §  Johannes  Ranke  found  the  mean  much 
higher :  one  kilogramme  produced  14  grammes  of  fluid 
bile,  and  0-44  grammes  of  dry  bile  in  the  twenty-four 

•  Friedliinder  and  Barisch,  Arch.f.  Aiiat.  Phys.  i860,  p.  655. 

f  Wolf,  Uwagi  nad  fzyologin  zolci,  Warschaw,  1S68.  Abstract  in  Ccntralbla{t 
f.  d.  med.  Wiss.  i86g,  p.  86. 

X  Bennett,  Rutherford,  and  Gamgee,  Report  of  the  Twenty-eighth  Meeting  of 
the  British  Association  for  the  Advancement  of  Science,  London,  1869,  p.  230. 

§  Westphalen,  Deutsches  Arch.f.  klin.  Med.  1873,  Bd.  xi.  p.  600. 


Comparison  of  Bile  of  Man  with  that  of  Dog.      103 

hours.*  This  observer  tries  to  bring  this  statement 
into  agreement  with  the  calculations  which  have  been 
made  from  animals.  Bidder  and  Schmidt  found  that 
one  kilogramme  in  a  cat  secreted  14*5  grammes  of  fluid 
bile  in  the  24  hours,  and  one  kilogramme  in  a  dog  20 — 28 
grammes.  For  the  same  animal  Nasse  found  12*2 — 28*4 
grammes,  figures  which  closely  correspond  with  those, 
of  Bidder   and   Schmidt.     Arnold's  fisfures  are  smaller: 

o 

8*1  to  1 1  "6  grammes  jf  while  Kolliker  and  Miiller's  are 
larger:  their  minimtcm  is  21*5  grammes  of  fluid  bile, 
with  0'75  gramme  of  dry  bile  ;  their  maximum  36"  16, 
with  i'i62  gramme  of  dry  bile.  All  these  are  from 
observations  on  dogs.  Johannes  Ranke  further  ob- 
serves that  Bischoff  and  Voit  in  their  observations  on 
the  same  animal  came  to  very  nearly  the  same  figure 
as  Ranke  did  with  man :  one  kilogramme  of  a  dog 
excretes  0*43  gramme  of  dry  bile,  while  one  kilogramme 
of  man  excretes  0*44  grm  of  dry  bile  in  the  24  hours, 
so  that  Ranke  concludes  that  man  excretes  as  a  mean 
about  840  grammes  of  bile  daily,  with  20  grammes  of 
solids.  I  must  own  that  I  do  not  feel  any  great  confi- 
dence in  Ranke's  figures,  as  he  shows  a  disposition  to 
use  the  figures  of  observers  when  they  corroborate  his 
own  ;  but  to  neglect  them  when  they  are  against  him. 
This  is  specially  to  be  noted  in  his  dealings  with  the 
amount  of  fluid  and  solid  bile,  when  he  passes  from  one 
to  the  other  according  as  the  figures  fall  into  agreement 
with  his  own  or  not. 

Dr.  George  Scott  found,  as  an  average  of  three 
days'  observations  on  one  dog,  that  each  kilogramme 
of  weight  secreted  23"i  grm.  of  fluid  bile,  and  1*13  grm. 
of  solid  bile,  in  the  twenty-four  hours. J      Ritter  gives, 

*  Johannes  Ranke,  Die  Blutvcrthcihtng,  Leipzig,  1871,  p.  151. 

f  All  these  figures  are  very  conveniently  given  in  a  table  put  together  by 
Kolliker  and  Miiller  {Verhandlungen  der  phys.  mcd.  Gesellschaft  in  Wiivzbiirg,  1856. 
Bd.  vi.  p.  461.)  This  table  is  given  at  p.  iii,  with  some  observations  which  have 
been  published  since  1856. 

X  George  Scott,  Beale's  Archives  of  Medicine,  1857,  vol.  i.  p.  218. 


104  Great  Variation  in  Amount  of  Bile. 

as  a  mean  of  a  week's  observation  on  one  dog,  iy'$  and 
18-75  grammes  of  bile  to  each  kilogramme  of  weight 
in  the  twenty-four  hours.*  The  Edinburgh  Committee 
gives  the  following  table  of  the  mean  amount  of  bile 
secreted  by  each  kilogramme  of  the  dogs  which  they 
observed  :t 


UMBER  OF  Dog. 

Fluid  Bile. 

Solid  Bile. 

grammes 

grammes 

I 

6-47. 

•412. 

I 

7-82. 

•28. 

2 

S-27- 

•34- 

3 

576. 

•293- 

4 

3-53- 

•146. 

5 

21-8. 

•801. 

6 

20-66. 

•818. 

7 

4-64. 

•23. 

8 

9-24. 

•305. 

9 

10-2. 

•58. 

The  variations,  even  in  observations  made  by  the 
same  observers,  are  here  very  great ;  and  show  how 
unsafe  a  course  it  is  to  draw  conclusions  from  a  small 
number  of  experiments. 

The  data  for  forming  an  opinion  on  the  amount  of  bile 
secreted  either  in  man  or  the  beasts  must  be  owned  to 
be  insufficient.  The  belief  now  prevalent  among  physi- 
ologists that  the  greater  part  of  the  bile  is  absorbed 
again  by  the  intestines,  and  excreted  again  by  the  liver, 
must  be  taken  into  account.  If  this  view  be  correct,  it 
must  be  hard  to  arrive  at  any  idea  of  the  amount  of  bile 
in  health  by  studying  the  amount  passed  out  from  a 
biliary  fistula.  The  bile  in  this  case  is  conveyed  away 
out  of  the  body,  does  not  enter  the  intestine,  and  so 
cannot  be  absorbed,  and  again  be  excreted  by  the  liver. 
To  judge   aright  of  the  amount   of  bile,   the   quantity 

*  Ritter,  Einige  Versnchc  itcbcr  die  Ahhiiugigkeit  dcr   Absonderungs-Grosse  der 
Gallc  von  der  Nahrung,  Diss.  Inaug.  Marburg,  1862,  p.  11. 
f  Edinburgh  Committee,  loc.  cit. 


Influence  of  Food  on  the  Bile.  105 

should  be  measured  as  it  is  secreted  by  the  liver,  and 
then  passed  again  to  the  duodenum. 

If  we  take  Westphalen's  mean,  500  C.C.  as  the  nor- 
mal flow  from  a  biliary  fistula,  and  the  solids  as  a  little 
over  2  per  cent,  the  daily  amount  of  solid  bile  will  be 
about  10  grammes,  or  somewhat  more.*  Of  these  solid 
matters,  the  bile  acids  will  form  about  one  half ;  choles- 
tearin  and  fats  about  one  gramme  ;  another  gramme  of 
pigments  and  mucus  ;  while  the  remainder  will  be  made 
up  of  inorganic  salts  ;  of  which  chloride  of  sodium  is 
the  greatly  preponderating  body,  about  2*4  grammes 
being  passed  in  the  24  hours.  Johannes  Ranke  found 
the  amount  of  solid  bile  in  his  patient  nearly  double 
these  figures  if  that  is  to  say,  of  solid  bile  20'6  grm.  a 
day,  of  which  the  bile  acids  formed  11  grammes,  the  fat 
and  cholestearin,  the  mucus  and  pigment,  and  inorgan- 
ic ashes,  all  three,  3*2  grm.  each.  The  sources  of  error 
which  may  have  crept  into  Johannes  Ranke's  estima- 
tions, and  which  may  have  made  it  too  high,  have 
already  been  pointed  out ;  but  it  is  worthy  of  note 
that  the  figures  correspond  very  nearly  to  the  amount 
at  which  Ernst  Bischoff  calculated  it  in  man  from  ob- 
servations on  animals.  J 

Influence  of  food  on  the  bile.  It  is  commonly  said, 
•from  experiments  on  animals,  that  the  taking  of  food 
into  the  stomach  is  followed  by  an  increase  in  the 
amount  of  bile.  In  Westphalen's  patient,  however,  the 
chief  meal  was  changed  several  hours,  yet  no  apparent 
alteration  in  the  amount  or  concentration  of  the  bile  fol- 
lowed. §  It  is  true  that  it  was  undesirable  to  allow  this 
patient  to  fast,  so  that  the  immediate  effect  of  food  after 
a  long  abstinence  could  not  be  ascertained.      In  Dr. 

*  Westphalen,  Deutschcs  Arch.f.  klin.  Med.  1873.  Bd.  xi.  p.  600, 
f  Johannes  Ranke,  Die  Blutvertheiliing,  Leipzig,  1871,  p.  150. 
+  Ernst  Bischoff,  Zeitschriftf.  rat.  Med.  1864,  Bd.  xxi.  p.  141, 
§  Westphalen,  Deiitsches  Archivf.  klin  Med.  1873,  Bd.  xi.  p.  601. 


io5  Influence  of  Food  upon 

Robinson's  case  it  is  distinctly  stated  that  the  flow  was 
more  rapid  soon  after  meals.* 

Blondlot,  noted  that  the  flow  of  bile  in  his  dog,  was 
much  more  abundant  after  food.  When  the  animal 
was  fasting,  it  sometimes,  but  not  always,  happened 
that  several  hours  would  go  by  without  a  drop  of  bile 
being  passed  ;  but  if  food  were  given,  the  bile  would 
flow  out  in  abundance  at  the  end  of  lo  minutes  or  a 
quarter  of  an  hour,  and  continue  to  flow  throughout  the 
time  that  digestion  was  going  on.-f 

Claude  Bernard  taught  that  the  secretion  of  bile  took 
place  after  digestion  was  over.  If  you  examine  an 
animal  with  a  biliary  fistula,  says  he,  you  see  that 
while  the  animal  is  fasting,  nothing  flows.  If  you  give 
the  creature  food,  the  flow  of  bile  does  not  begin  at 
once,  but  at  the  end  of  a  certain  time,  and  it  persists 
after  digestion  is  finished.  In  fact,  the  bile  of  one 
digestion  is  only  used  in  the  next.  The  bile  is  collected 
in  the  bladder,  which  is  emptied  during  digestion,  but 
is  filled  before.  J 

Bidder  and  Schmidt  give  the  following  as  the  result 
of  their  experiments  on  cats :  the  amount  of  bile  is 
increased  in  the  first  hour  after  a  meal,  and  before 
the  food  can  have  been  absorbed  into  the  blood.  This 
is  apparently  simply  a  consequence  of  the  increased 
flow  of  blood  to  the  digestive  organs.  The  increase  of 
secretion  reaches  its  highest  point  12  to  15  hours  after 
the  meal  have  been  taken,  when  it  is  probable  that  all 
the  food  has  been  completely  digested  and  absorbed  into 
the  blood  mass.§     From  this,  the  amount  of  secretion 

*  Robinson,  Med.  Chir.  Trans.  1852,  Vol.  xxxv.  p.  473. 

f  Blondlot,  Essai  siir  Ics  fonctiuns  dufoic,  Paris  and  Nancy,  1846,  p.  62. 

\  Claude  Bernard,  Lci;oiis  <?-c.  liqnidcs  dc  Vor^anisnic,  Paris.  1859,  t.  ii.  p.  202. 

§  The  same  year  that  Bidder  and  Schmidt's  book  was  published,  C.  G.  Leh- 
mann  expressed  the  opinion  that  more  bile  ought  to  be  secreted  10  hours  after  food 
than  5  hours  after;  because  there  is  more  change  in  the  blood  later  than  earlier. 
{yoiirntil  dc  Plianii.  ct  dc  Cliimic,  1852,  t.  xxi.  p.  399.) 


the  Amount  of  Bile  Secreted.  107 

sinks;  and  In  24  hours  after  the  meal,  it  has  fallen  be- 
low the  amount  which  it  showed  immediately  after  the 
taking  of  food.* 

Arnold  states  that  he  found  the  greatest  amount  of 
bile  always  to  make  its  appearance  in  the  first  hours 
after  the  meal  had  been  taken.  The  figures  which  he 
gives  are  as  follows  if 


I  hour 

5-257 

gframmes 

2  hours 

5-346 

3     „ 

■     5'I2I 

4     ,» 

4-612 

5     „ 

4-146 

6    „ 

3-504 

7    V 

3-583 

8     „ 

3-817 

9          M 

4-344 

10    „ 

4-012 

II     „ 

3-612 

Arnold's  experiments  were  made  on  one  dog,  and 
there  appear  to  have  been  only  two  sets  of  observations 
on  this  point, 

Kolliker  and  Miiller  find  that  a  very  small  amount  of 
bile  is  secreted  in  the  first  and  second  hour  after  food. 
Sometimes  the  amount  is  even  less  than  in  the  igth  to 
25th  hour.  In  the  3rd  to  5th  hour,  they  found  almost 
without  exception  an  increase  of  the  secretion.  Indeed 
in  two  cases  the  fifth  hour  showed  the  highest  amount, 
while  in  the  others  the  maximum  was  seen  from  the 
6th  to  8th  hour.  After  this,  the  amount  again  fell 
until  the  minimum  was  reached  in  the  19th  to  25th 
hour. J 

*  Bidder  and  Schmidt,  Die  Verdanungssaefte,  Mitau  and  Leipzig,  1852,  p.   144. 
t  Friedrich  Arnold,  Zur  Physiologic  der  Galle,  Mannheim,  1854,  p.  16. 
X  Kolliker  and  Miiller,  Verhandlungen  der  phys.-mcd.  Gcselhchaft  in   Wnrzburg, 
1856,  Bd.  vi.  p.  454. 


io8 


Influence  of  Food  upon 


ist  DOG. 

1 

2nd  DOG 

3rd  DOG 

5th  DOG. 

Hour 
after 
food. 

I  St  Series.                   2nd  Series. 

B 

Liquid 

le. 
Solid 

Bile. 

Liquid      Solid 

Bile. 
Liquid      Solid 

Bile. 
Liquid      Solid 

Bile. 
Liquid     Solid 

I —  2 

i'45o 

0.051 

I-22I 

0-040 

0-823 

0-035 

0-675 

0.026 

1-538 

0-053 

3—  5 

1-407 

0-047 

1-462 

0-042 

I-198 

0-044 

O-9S6 

0-034 

2-222 

0-060 

6—  8 

1-514 

0-048 

1705 

0-046 

1-242 

0-047 

1-093 

0-035 

1.889 

0-054 

g— 14 

1-368 

0-041 

15—18 

1-435 

0-043 

15 — 20 

1-085 

-040 

16 — 22 

1-320 

0-051 

19—21 

i-iig 

0-036 



20 — 24 

1-203 

0.047 

21 — 25 

0-750 

0-030 

The  figures  are  grammes. 

These  observations  of  Kolliker  and  Miiller  seem  to  be 
certainly  more  worthy  of  confidence  than  those  which 
went  before  them.  They  were  made  on  the  same 
animals,  not  as  in  Bidder  and  Schmidt's  cases,  on 
different  animals  at  different  times  of  digestion. 

Voit,  without  giving  further  details,  says  that  the 
observations,  which  he  had  made  upon  Bischoff's  dog 
with  a  biliary  fistula,  showed  that  the  secretion  of  bile 
rose  immediately  after  taking  nourishment.  The  maxi- 
mum arrived  in  2  to  4  hours.  The  solids  of  the  bile 
were  increased  as  well  as  the  fluid  part.* 

In  guinea  pigs,  it  was  noted  by  Heidenhain  that  no 
such  great  increase  of  the  flow  of  bile  took  place  after 
food.  Nor  did  the  flow  seem  much  decreased  by  fast- 
ing. It  was  only  when  the  guinea  pig  had  fasted  for 
66  hours  that  any  decrease  was  noted.  The  guinea 
pig  is  a  vegetable  eater,  and  his  stomach  remains  full 
of  food  long  after  the  last  meal :  so  the  process  of  diges- 

*  Karl  Voit,  Pliys.-  client.  Untcrsuclntngcn,  Augsburg,  1857,  P-  4i- 


the  A  mo^mt  of  Bile  Secreted  log 

tion  is  always  going  on,  and  in  this  way  Heidenhain 
explains  the  difference  between  flesh  eaters  and  vege- 
table eaters.* 

Some  experiments  of  Ritter's  are  an  attempt  to  re- 
concile the  varying  statements  of  other  observers.  He 
made  six  observations  on  his  dog  and  gives  the  following 
as  the  result  of  his  labours  on  this  point:  that  after  food 
there  are  two  maxima  of  secretion  of  bile  ;  the  former  of 
these  falls  in  the  first  or  second  hour  after  the  meal ; 
the  latter  has  no  such  precise  time  of  appearance  ;  the 
less  the  amount  of  nourishment,  the  earlier  its  appear- 
ance ;  the  greater,  the  later. f 

Influence  of  the  amount  of  food  on  the  bile. — It  has  been 
seen  that  Kolliker  and  Miiller  found  the  amount  of  bile 
to  fall  to  its  lowest  point,  ig  to  25  hours  after  a  meal ; 
Bidder  and  Schmidt  saw  that  by  withholding  nourish- 
ment from  cats  the  amount  of  bile  sank  to  a  minimum ;% 
240  hours  after  the  last  meal,  the  amount  of  fluid  bile 
was  only  94  milligrammes  in  an  hour,  and  of  solid  bile 
but  seven  milligrammes. 

The  Edinburgh  Committee  saw  a  marked  effect  follow 
the  withholding  of  food  from  a  dog.  Only  liver  was  given 
as  food,  and  no  water;  the  amount  of  bile  fell  to  I04"8 
grammes  in  the  24  hours  against  140  grammes  for  the 
two  foregoing  days.  The  bile  solids,  however,  rose  to 
7'73  grammes,  about  one  half  more  than  they  had  been; 
and  this  was  due  to  a  great  rise  in  the  organic  consti- 
tuents of  the  bile  as  the  inorganic  salts  remained  the 
same  in  amount.  The  next  day,  only  water  was  allowed, 
and  the  amount  of  fluid  bile  fell  to  41 '6  grammes,  and 
the  solids  to  277  grammes. § 

From  these   observations  it  may  be  looked  upon  as  a 

*  Friedlander  and  Barisch,  Arch.f.  Anat,  Phys.  i860,  p.  654. 
f  Joseph  Franz  Ritter,  Einigc  Vcrsuche  ilber  die  Abhdngigkcit  d.  Ahsondcvungs- 
Grosse  der  Galle  von  der  Nahning,  Diss.  Inaug.  Marburg,  1862,  p.  27. 
+  Bidder  and  Schmidt,  op.  cit.  p.  144. 
§  Edinburgh  Committee,  op.  cit.  p.  222. 


no  Influence  of  Food  npon 

probable  opinion  that  the  withholding  of  food  decreases 
the  amount  of  fluid  bile  secreted,  and  possibly  also  of 
the  solid  bile. 

Bidder  and  Schmidt  also  fed  two  cats  abundantly 
with  meat ;  one  took  in  four  days  no  less  than  a  half 
of  its  own  weight ;  the  other  took  one-third  of  its  own 
weight  in  two  days.  The  amount  of  bile  secreted 
by  each  animal  was  almost  the  same.  For  every  kilo- 
gramme of  cat,  there  was  secreted  in  one  hour,  in  the 
first  cat,  2*055  grm.  of  fluid  bile  with  -172  grm.  of  solids, 
and  in  the  second  cat  i'g65  of  fluid  bile  with  -178  grm. 
of  solids.  The  average  which  they  give  for  cats  is  that  one 
kilogramme  secretes  in  every  hour  '608  grm.  of  fluid  bile 
with  34  milligrammes  of  solids.  So  that  if  these  two  ex- 
periments on  cats  represent  a  general  rule,  a  great  in- 
crease in  the  secretion  of  bile  takes  place  on  an  abund- 
ant diet. 

In  Arnold's  experiments,  the  dog,  weighing  775  kilo- 
grammes, was  fed  daily  with  750  grm.  of  meat.  The 
amount  of  bile  daily  secreted  was  on  an  average  go"295 
grm.  One  kilogramme  of  the  dog,  therefore,  on  this  diet 
of  meat  secreted  11  "65  grm.  of  bile  in  the  24  hours.  One 
gramme  of  bile  was  secreted  in  twenty-four  hours  for 
every  8*306  gramme  of  meat  given.  When  the  same  dog 
was  daily  fed  on  470  grm.  of  rye  bread,  the  weight  of  the 
dog  being  7"8i2  kilogramme,  there  was  secreted  of  bile 
on  an  average  63*024  grm.  Therefore  on  this  amount  of 
rye  bread  one  kilogramme  of  the  dog  secreted  8*067  gi'i'^T^- 
in  the  24  hours.  One  gramme  of  bile  was  secreted  in 
the  twenty-four  hours  for  every  7*459  gramme  of  bread 
given.* 

The  following  table  has  been  drawn  up  by  Kolliker 
and  Miiller  and  is  a  convenient  summary  of  what  was 
done  by  these  observers  and  those  who  had  gone  before 
them,   of  the   amount   of  bile   secreted   under  differing 

*  Friedrich  Arnold,  Zur  Pliysiulogie  der  Galle,  Mannheim,  1854,  p.  16. 


the  A  mount  of  Bile  Secreted. 


Ill 


For   every   kilo- 

For    every     100 
grammes  of  food 

Name  of  Observer. 

gramme  of    dog 
there  was  secret- 
ed in  24  hours  : 

Food  for  every  kilogramme  of 
weight. 

in  the  24  hours 
there    was     se- 
creted of 

Fluid 

Solid 

Fluid 

Solid 

Bile 

Bile 

Bile 

Bile 

Gram.mes. 

Grammes. 

Grammes. 

I.  Nasse 

I9"2 

0-685 

155    flesh    meat 

12-3 

0-440 

2.          „              .... 

22-8 

0700 

208       ,, 

II-OI 

0-337 

3-       ..          .... 

23-1 

0784 

260        ,,         ,, 

8-9 

0-300 

24-0 

0765 

meat    ad     lib. 

4.       „          .... 

28-4 

0760 

,,        ,,         ,, 

5-       >)          .... 

6.  Arnold 

II-5 

o'373 

75     flesh    meat 

12-0 

0-385 

7.  Kolliker  &  Muller. 

327 

i'034 

8.       „ 

32-6 

1-290 

98     flesh    meat 

9- 

26-1 

1-013 

92        „ 

28-56 

1-094 

10.       „ 

21-5 

0-748 

94 

22-85 

0-792 

II.       )>                  11 

36-r 

1-162 

64       n          „ 

56-50 

1-816 

12.       ,,                  „ 

53-6 

1-683 

94       i> 

56-7 

1-79 

13.  Bidder  &  Schmidt. 

I5'9 

0-840 

1   32       „         „ 
I      1-7  fat 

49-3 

2608 

14-       .. 

167 

0-696 

f    17     flesh 
\     7-8  milk 

83-5 

3-48 

15.       M 

24-5 

1-176 

f   79     flesh 
[     8     bread 

25-7 

1-23 

16.       „ 

287 

1-268 

f    66     flesh 
i      8     bread 

35-1 

1-54 

17.  Nasse 

177 

0-446 

( 100     flesh 
( 100     bread 

18.       „         .... 

17-9 

0-400 

f 130     flesh 
\  100     bread 

19.       „          .... 

I2"2 

0-505 

87        » 

13-9 

0-575 

20.  Arnold 

8-1 

0-215 

60        ,, 

13-4 

0-353 

21.  Kolliker  &  Miiller. 

32-1 

(   37-9  bread 
(.   94     c.c.  milk 

22.  Carl  Voit.    ... 

II-8 

0-503 

48-2  flesh 

24-5 

1-115 

23.       „       „       ... 

IO-8 

0-5 

54 

20-0 

0-914 

24.  Dr.  George  Scott. 

23-1 

1-13 

(■   62-7  flesh 
\    70     milk 

25.  Ritter 

1875 

183-4  flesh 

10-22 

26.       , 

17-5 

170-6     ,, 

10-29 

27.       ,,          .... 

15-2 

138-8     „ 

11-007 

28.       „          .     .  •  .     . 

13-4 

103-5     .. 

13-10 

29.       „          .... 

IO-5 

70-5     .. 

14-81 

30.  Edinburgh    Com- 

mittee. .     .     . 

6-47 

0-412 

12-3  dry  food 

52-18 

3-32 

31-          n 

7-82 

0-28 

13-6     „     „ 

57-21 

2-05 

32.     „ 

5-27 

0-34 

67     „     .> 

33-       ., 

5-47 

0-293 

10-9     „     ,, 

58-9 

3-165 

34-       ., 

3-53 

0-146 

8-8     „     „ 

40-13 

2-148 

35-       „ 

21-8 

o-8oi 

23-4     ..     " 

92-9 

3-49 

36.       „ 

4-64 

0-23 

19-34  ..     " 

23-99 

1-21 

37-       .. 

9-24 

0-305 

9-3       n       .. 

51.84 

1-714 

112  Influence  of  Food  upon 

amounts  of  food.*      The  figures  of  the  authors  since 
1856  have  been  put  together  for  this  work. 

KolHker  and  Miiller  say  very  truly  that  on  first  look- 
ing through  this  table  it  does  not  seem  possible  to 
draw  any  general  conclusions  from  it.  They  think  that 
there  is  a  certain  correspondence,  however,  between  the 
conclusions  of  Nasse  and  Arnold  on  the  one  side  ;  and 
Bidder  and  Schmidt  with  Kolliker  and  Miiller  on  the 
other.  The  two  first  authors  find  the  amount  of  solid 
bile  secreted  by  one  kilogramme  of  dog  in  24  hours,  on 
different  kinds  of  food,  to  vary  between  0'2i5  and  o'785 
grm. ;  the  latter  observers  find  it  between  0'6g6  and  i'2go 
grm.  If,  however,  the  amount  of  fluid  bile  secreted  in  the 
24  hours  for  every  kilogramme  of  dog  be  compared,  a 
different  aspect  is  given  to  matters ;  Nasse  gives  it 
as  from  I2'2  to  28-4  grm.  ;  and  Bidder  and  Schmidt 
between  15*9  and  28*7  :  a  close  correspondence.  But 
the  solid  bile  is  that  which  is  of  most  importance ;  and  the 
higher  figures  of  Nasse  correspond  to  a  higher  amount 
of  food,  while  the  dogs  of  Bidder  and  Schmidt  were  fed 
rather  low.  The  dogs  of  Kolliker  and  Miiller  were, 
however,  better  fed  than  those  of  Bidder  and  Schmidt, 
yet  the  amount  of  dry  bile  in  Bidder  and  Schmidt's 
dogs  was  nearly  on  a  level  with  Kolliker  and  Miiller's. 
It  would  follow  that  the  observations  of  these  four 
writers  have  a  real  correspondence  with  each  other. 
This  is  still  more  marked,  as  is  also  the  agreement 
between  Arnold  and  Nasse,  when  the  amount  of  bile 
secreted  for  each  100  grm.  of  food  is  considered.  Nasse 
and  Arnold  give  between  8*g  and  lyg  grm.  of  fluid  bile 
with  0*300  to  o'575  dry  bile  for  every  100  grm.  of  food. 
Bidder  and  Schmidt  with  Kolliker  and  Miiller  on  the 
other  hand  give  much  higher  figures:  22*85  to  83'5  grm. 
of  fluid  bile  with  0*792  to  3*48  of  dry  bile  to  every  100 
grm.  of  food. 

*  Kolliker  and   Miiller,  Vcrhaiidluugcii  d.  phys.  mcd.  Gcsclhchaft  in  Wilrzburg, 
1856,  Bd.  vj.  p.  461. 


the  Amount  of  Bile  Secreted. 


113 


I  am  more  inclined  myself  to  agree  with  the  first 
paragraph  of  Kolliker  and  Miiller's  argument,  and  to 
think  that  but  few  general  conclusions  can  be  drawn 
from  this  table,  even  if  the  more  recent  observations  be 
taken  into  the  service.  The  variations  in  the  figures  of 
the  Edinburgh  Committee  are  very  considerable;  a 
large  amount  of  bile  was  secreted  when  either  little  or 
much  food  was  given. 

Ritter,  a  pupil  of  Nasse,  made  under  his  guidance 
many  careful  and  interesting  observations  on  a  dog,  in 
whom  he  had  established  a  biliary  fistula.  He  found 
that  by  decreasing  the  daily  amount  of  food,  the  amount 
of  bile  also  decreased.*  For  example:  the  dog,  fed  on 
2500  grm.  of  meat  daily,  produced  on  an  average  255'5 
grm.  of  bile  in  the  24  hours.  Fed  only  on  1000  grm. 
of  meat  daily,  he  produced  147' i  grm.  of  bile  in  the  24 
hours.     The  following  table  shows  the  exact  figures  : 


Weight  of  Dog  before  the  Biliary  Fistula  was  estab- 
lished =  13-5  kilogrammes. 


Series  of  experi- 
ments. 

Food  in 
fresh  meat. 

Average 

weight    of 

animal. 

Average 
amount  of 
bile   in  24 
hours. 

Average  se- 
cretion  of  1 
kilogramme 
in  24  hours. 

Amount  of 
food  in  meat 

for     every 
kilogramme 
of    the     dog 
in  24  hours. 

For  every 
kilogramme 

of  meat 

there  were 

secreted  in 

24  hours, 

of  bile. 

I. 
2. 

3- 
4- 

5- 

2500 
2500 
2000 
1500 
1000 

13-629 

14-656 

14-52 

i4'544 

I4-I75 

255-5 

257-3 

220-15 

196-5 

148-I 

18-75 

17-5 
15-2 

134 
10-5 

183-4 
170-6 
138-8 
103-5 

70-5 

102-2 

102-9 

110-07 

131-0 

I48-I 

The  weights  in  this  table  are  in  grammes. 

The  first  series  of  experiments  lasted  uninterruptedly 
for  7  days  :  the  second  for  8  days  :  the  third  for  5  days  : 
the  fourth  also  for  5  days,  but  with  an  interlude  of  3 

*  Joseph  Franz  Ritter,  Eiiiigc  Vcrsuche  i'lbcr  die  Ablidngigkeit  dcr  Absondcruiig 
Grosse  dcr  Galle  von  der  Nahniiig,  Diss.  Inaug.  Marburg,  1862,  pp.  10,  ct  scqq. 

I 


114  Influence  of  the  Kind  of  Food 

days  between  the  2nd  and  3rd  day  of  observation  ;  the 
fifth  for  4  days  without  interruption. 

Influence  of  the  kind  of  food  upon  the  secretion  of  the 
bile. — Bidder  and  Schmidt  fed  two  cats  only  on  fat  or 
oil  for  five  or  three  days,  and  a  third  was  fed  abundantly 
for  several  days  on  very  fat  meat.  The  first  cat  yielded 
by  kilogramme  in  an  hour  0-588  to  0'i28  grm..  of  liquid 
bile,  and  62  to  16  milligrammes  of  solid  bile ;  the 
second,  0"347  to  0*21 1  grm.  of  fluid  and  39  to  15  milli- 
grammes of  solid  bile.  The  third  cat,  fed  on  very  fat 
meat,  yielded  0*327  to  O'iSi  grm.  of  fluid  bile  and  28 
to  16  milligrammes  of  solid  bile.*  These  figures  are  very 
little  above,  if  not  equal  to,  those  given  by  cats  who 
had  fasted  for  days.  It  follows  that,  in  animals  fed 
solely  on  fat,  the  secretion  of  bile  falls  to  a  minimum. 
These  observers  also  noted  that  those  animals,  with 
little  fat  under  their  skin,  often  gave  a  more  abundant 
secretion  of  bile  than  fat  ones.*!* 

Yet,  according  to  some  experiments  of  Nasse,  it 
would  seem  that  if  fat  be  added  to  the  ordinary  food, 
the  amount  of  bile  secreted  is  raised.  For  five  days  he 
fed  a  dog  with  meat  and  fat,  and  the  secretion  attained 
the  amount  of  2i9"8  grm.  in  24  hours.  The  same 
amount  of  meat,  but  without  the  fat,  was  given  for  the 
five  following  days,  and  the  secretion  fell  to  59"26  in  the 
24  hours.  Then  he  gave  fat,  as  much  as  the  animal 
would  take  with  the  other  food,  for  four  days  ;  and  the 
amount  of  bile  rose  again  to  .206*  13  in  the  24  hours. 
The  bile  soon  after  fell  again  in  amount,  as  the  creature 
lost  its  appetite  and  refused  its  food.  J  The  dog  was 
therefore  probably  out  of  health  during  the  observations. 

Ritter  has  continued   some  observations  in  the  same 


*  Bidder  and  Schmidt,  op.  cit.  p.  148. 
t  p.  236. 

X  Hermann  Nasse,  Commcnlat'w  de  bills  qiiotidle  a  cane  secreta  copla  et  indole, 
Marburg,  185 1,  p.  14. 


itpon  the  A  mount  of  Bile  Secreted. 


115 


direction,  but  without  the  striking  results  obtained  by 
Nasse.  He  did  not,  however,  feed  his  animal  for 
several  days  without  or  with  fat :  but  gave  fat  about 
every  alternate  day.  There  is  but  little  variation  in  the 
amount.* 


Grammes 

Date. 

Food.                        ,           of 

BILE    IN    24   HOURS 

Dec.  26. 

1000  grm.  of  meat  without  fat. 

170-3 

27. 

same  with  125  grm.  of  hog's-fat. 

213  grm. 

28. 

same. 

212-3 

Jan.    II. 

1500  grm.  of  meat  without  fat. 

182-6 

12. 

same. 

207-2 

13- 

same  with  125  grm.  ofhog's-fat. 

180 

14. 

same. 

202-8 

IS- 

same  without  fat. 

216-8 

16. 

750  grm.  meat  without  fat. 

171-0 

.    17. 

same. 

162-8 

18. 

same. 

1 24- 1 

19. 

same  with  125  grm.  ofhog's-fat. 

132-0 

20, 

same. 

138-6 

21. 

same  without  fat. 

130-6 

22. 

same. 

.    123-6 

The  belief  that  fat  joined  to  other  food  causes  an 
increase  of  bile  is  not  supported  by  these  figures. 

The  last  experiments  made  by  Ritter  were  the  sub- 
stitution of  potatoes  for  flesh  in  the  diet  of  his  dog ;  the 
amount  of  bile  at  once  sank  and  continued  low,  whether 
fat  were  or  were  not  given  with  the  potatoes.  The 
amount  of  bile  secreted  in  the  twenty-four  hours  varied 
in  four  experiments  from  46  to  66*  i  grm.f 

The  observations  of  Arnold,  who  found  a  lower  amount 
of  bile  secreted  when  the  dog  was  fed  on  rye  bread  than 
when  fed  on  meat,  have  already  been  quoted.  The 
proportion  for  each  kilogramme  was  11 '65  grm.  of  bile 
on  flesh,  to  8"667  on  bread, J  a  considerable  decrease. 

*  Ritter,   Einige   Versuche  i'lber  die  Absondenings-Grosse  der  Galle    von    der 
Nahnmg,  Diss.  Inaug.  Marburg,  1862,  p.  28. 
■(    Ritter,  op.  cit.  p.  32. 
\  Arnold,  Zur  Physiologic  der  Galle,  Mannheim,  1854,  p.  16. 

I  2 


ii6  Difference  between  Day  and  Night. 

And  Karl  Voit  found  about  the  same  amount  as  Arnold 
when  his  two  dogs  were  fed  only  on  meat;  ii'77  and 
1077  grm.  of  bile  secreted  by  the  kilogramme  in  the  24 
hours.* 

If  the  figures  of  Ritter  be  looked  through,  it  is  evident 
that  most  bile  was  secreted  when  the  animal  was  most 
abundantly  supplied  with  flesh.  He  does  not  seem  to 
have  tried  feeding  the  animal  with  an  equal  weight  of 
bread.  When  fed  with  potatoes  in  weight  equal  to 
that  of  meat,  the  secretion  certainly  fell  very  much 
lower  (4:1). 

In  looking  at  the  table  from  Kolliker  and  Miiller,  it  is 
hardly  possible  to  draw  any  conclusion  ;  if  anything, 
the  figures  would  seem  to  show  that  as  much  solid  bile 
is  secreted  on  a  low  diet  as  on  a  full  one.  The  highest 
amount  of  solid  bile  secreted  was  when  the  dog  was 
fed  on  but  17  grm.  of  meat,  and  7*8  of  milk  for  every 
kilogramme. 

It  would  seem  a  priori  probable  that  more  bile  should 
be  secreted  on  a  high  than  a  low  diet,  and  also  that  a 
nitrogenous  diet  should  favour  the  secretion,  as  the  bile 
acids  contain  so  much  nitrogen.  The  whole  of  Ritter's 
experiments  are  rendered  much  less  valuable  by  his 
neglect  of  the  solid  constituents  of  the  bile  ;  a  trouble- 
some estimation,  it  will  be  owned,  but  one  which  cannot 
be  avoided  in  investigations  of  this  sort. 

Difference  between  night  and  day. — Westphalen  noted 
in  his  patient  that  the  lowest  amount  of  fluid  bile  in  the 
twenty  hours  was  always  secreted  in  the  night,  between 
2  and  6  a.m.  It  contained,  however,  a  far  larger  per- 
centage of  solids. t  Nasse  had  before  remarked  that 
in  the  dog  the  amount  of  bile  was  less  at  night  than  in 
the  day,  although  if  the  dog  were  fed  night  and  morning 
instead   of  at  mid- day,  or  had  taken  a  great  quantity  of 

•  Karl  Voit,  Phys.-Chcm.  Untcrsuchiingen,  Augsburg,  1857,  PP-  3^  ^"^  4°- 
f  Westphalen,  Dciitschcs  Arch.f.  klin.  Med.  1873,  Bd.  xi.  p.  595. 


Influence  of  Drink  on  the  Bile.  117 

food,  this  decrease  was  not  noticed.  During  the  night 
it  appears  that  the  percentage  of  sohd  matters  was 
usually  greater  than  during  the  day.*  Ritter,  Nasse's 
pupil,  repeated  this  observation  in  1862.! 

Influence  of  drink  on  the  secretion  of  the  bile. — In 
Westphalen's  patient  no  increase  in  the  bile  followed 
the  drinking  of  a  considerable  quantity  of  water  on  two 
following  days.  There  was  no  noteworthy  dilution  of 
the  secretion,  although  the  amount  of  urine  was  doubled, 
and  its  specific  gravity  sank  from  1021  to  loii.J  On 
animals,  however,  quite  the  opposite  has  been  seen. 
Bidder  and  Schmidt  noted  that  in  three  dogs  the 
amount  of  bile  was  doubled  or  trebled  very  shortly 
after  drink  was  given  ;  not  merely  the  water  but  the 
solid  contents  of  the  bile  were  increased. §  In  one  dog, 
however,  this  result  did  not  always  take  place  ;  for  out 
of  five  experiments  it  was  not  seen  in  two  and  but 
slightly  in  one.|| 

Nasse  reports  shortly  that  if  the  dog  took  a  great 
quantity  of  water  with  the  food,  there  was  a  larger 
secretion  of  bile. ^     Arnold  says  the  same  thing.** 

Rohrig  also  found,  both  in  dogs  and  rabbits,  that  the 
injection  of  warm  water  into  the  small  intestine  had  a 
marked  effect  on  the  amount  of  secretion.  The  effects 
of  a  second  injection  were  more  lasting  than  of  the 
first. ft  Only  the  amount  of  bile  was  estimated  in 
Rohrig's  experiments,  not  the  solid  contents. 

Mosler  injected  water  into  the  veins,  but  no  account 
is  given  of  the  amount  of  the  secretion  if  increased  or 
decreased. JJ 

*  Nasse,  Comment  de  bUis  quotidie,  etc.  Marburg,  1851,  p.  ig. 

f  Ritter,  Einige  Versuche  11.  s.  w.     Diss.  Inaug.  Marburg,  1862,  p.  23. 

X  Westphalen,  Deutsches  Arch./,  klin.  Med.  1873,  Bd.  xi.  p.  600. 

§  Bidder  and  Schmidt,  op.  cit.  pp.  166  and  168. 

il  p.  181. 

IT  H.  Nasse,  Commentatio  de  bilis  quotidie,  etc.  p.  18. 

**  F.  Arnold,  Ziir  Physiologic  der  GaUe,  Mannheim,  1854,  p.  17. 

f  f  Rohrig,  Strieker's  Med.  Jahrbb.     Wien,  1873.  p.  246. 

XX  Mosler,  Arch.f.  path.  Anat.  1858,  Bd.  xiii.  p.  32. 


ii8  Blood  Pressure  in  the  Liver. 

Prince  Tarchanoff  injected  200  C.C.  of  distilled  water 
into  the  jugular  vein  of  a  dog  and  found  a  great  in- 
crease in  the  amount  of  fluid  bile  and  of  the  pigment.* 

Socoloff,  in  two  experiments  also  made  in  Hoppe- 
Seyler's  laboratory,  came  to  results  which  agree  with 
those  of  Westphalen  rather  than  with  those  of  Bidder 
and  Schmidt  and  the  other  observers.  He  injected  50 
C.C.  of  I  per  cent,  solution  of  common  salt  into  the 
stomach  of  a  dog,  and  100  C.C.  of  a  like  solution  into 
the  crural,  later  on.  Rather  a  fall  than  an  increase  was 
noted,  especially  in  the  second  case,  both  in  the  amount 
of  fluid  and  solid  bile.f 

Heidenhain  agrees  with  Bidder  and  Schmidt  that  an 
increase  of  bile  takes  place  in  most  cases  ;  but  not  in 
all.  Out  of  ten  there  were  two  in  which  no  increase  of 
the  flow  took  place. ^ 

Influence  of  an  increase  or  decrease  of  the  blood  pressure 
in  the  liver  on  the  secretion  of  bile. — Heidenhain,  with  the 
assistance  of  his  two  pupils,  Korner  and  Strube,  found 
that  the  sudden  raising  of  the  blood  pressure  by  inject- 
ing 2V  or  5^0  of  their  weight  of  water  into  the  veins  of 
guinea  pigs,  caused  in  the  first  hour  a  decrease  in  the 
amount  of  bile.  The  decrease  was  always  present  in 
the  first  hour,  and  in  4  of  the  7  experiments  lasted  for 
some  hours,  while  in  three  experiments  it  soon  began 
to  rise  again.  In  these  four  experiments  the  fall  was 
considerable  ;  it  was  smaller  in  the  last  three. 

On  lowering  the  blood  pressure  by  bleeding  the 
guinea  pig,  or  by  tying  one  of  the  mesenteric  veins  or 
the  splenic  vein,  there  followed  a  like  decrease  in  the 
amount  of  bile  collected. § 

*  Johannes,  Fiirst  Tarchanoff,  Arch.f.  d.  ges.  Phys.  1874,  Bd.  ix.  p.  330. 

f  Socoloff,  Arch.  f.  d.  ges.  Phys.  1875.  Bd.  xi.  p.  176. 

J  Korner  and  Strube,  Stndien  d.  phys.  Inst,  zu  Brcslau,  Leipzig,  1863,  Heft  ii. 
p.  94. 

§  Heidenhain,  Studicn  d.  phys.  Iiistit.  zu  Breslaii,  Leipzig,  1863,  Heft  ii.  p.  94, 
Of.  below  (p.  122.)  the  important  experiments  on  irritation  of  the  spinal  chord,  and 
and  consequent  changes  in  the  blood  pressure  in  the  liver. 


Effects  of  Muscular  Contraction.  i  ig 

Hermann  Nasse  says  that  no  change  in  the  secretion 
of  the  bile  followed  the  loss  of  a  ''  few  ounces"  of  blood 
from  the  jugular  vein.* 

Johannes  Ranke  found  that  the  secretion  of  bile  in  a 
guinea  pig  absolutely  stopped  when  the  creature  had 
lost  J  of  the  weight  of  its  blood. f  He  also  says  that 
the  secretion  begins  again  if  fluids  be  injected  into  the 
veins  after  this  loss  of  blood.  J  Rohrig  found  the  secre- 
tion of  bile  in  two  dogs  to  be  brought  to  an  end  by  a 
bleeding ;  the  injection  of  water  into  a  mesenteric  vein 
again  made  the  secretion  to  flow,  but  only  for  a  very  few 
seconds. § 

Influence  of  the  contractions  of  muscles  on  the  secretion  of 
bile. — The  relation  of  bodily  exercise,  or  of  the  contrac- 
tion of  muscles,  to  the  metamorphoses  of  the  tissues  is 
one  of  the  most  interesting  problems  in  physiology. 
Johannes  Ranke  has  attempted  to  make  out  the  in- 
fluence of  muscular  contraction  on  the  bile,  and  comes 
to  the  conclusion  that  the  change  in  the  distribution  of 
blood  to  the  muscles  corresponds  to  a  change  in  the 
functions  of  the  liver ;  and  that  when  the  muscles  from 
their  contraction  contain  more  blood,  less  blood  flows 
to  the  liver,  which  therefore  does  less  work ;  thus  the 
muscular  contraction  has  all  the  effect  of  bleeding.  || 
Johannes  Ranke's  experiments  seem  somewhat  open 
to  criticism.  The  intestines  were  considerably  inter- 
fered with,  and  a  disturbance  in  the  circulation  might 
thus  be  readily  set  up.  And  the  application  of  the 
electricity  seems  to  have  followed  at  very  short  inter- 
vals, so  that  it  would  be  hard  to   distinguish  between 


*  Hermann  Nasse,  Commcntatio  de  bills  quotidie  a  cane  secreta  copia  et  indole. 
Marburgi,  1851,  p.  12. 

t  Johannes  Ranke,  Die  Bliitvertheilung,  Leipzig,  1871,  p.  190. 

X  p.  117- 

§  Rohrig,  Strieker's  Med.  Jahrhb.  Wien,  1873,  p.  246. 

I!  Johannes  Ranke,  op.  cit.  p.  117. 


I20  Nervous  Influences  upon  the  Bile. 

the    effects  of  the   contraction    and  exhaustion  of  the 
muscles. 

Inspiratory  movements  and  struggles  are  noted  by 
many  writers  as  causing  an  increased  flow  of  bile  from 
a  biliary  fistula :  so  vomiting.  These  phsenomena  are 
not  due  to  an  increased  secretion,  but,  the  pressure 
within  the  belly  being  raised,  the  bile  already  se- 
creted and  in  the  ducts  is  expelled.  The  Edinburgh 
Committee  noted  an  increased  flow-  of  bile  during  the 
first  half  hour  that  the  dogs  were  taken  from  their 
cages  and  let  run  about.* 

Influence  of  the  nerves  on  the  secretion  of  bile. — Schih 
divided  in  dogs  and  cats  the  nerves  which  accompany 
the  hepatic  artery,  but  found  no  change  in  the  secretion 
of  bile.t  Rohrig  found  no  change  on  division  or  irrita- 
tion of  the  vagus.X 

Heidenhain's  pupils,  Goldschmidt,  Hausmann  and 
Lissa,  found  that  in  guinea  pigs  a  considerable  de- 
crease in  the  secretion  of  bile  followed  the  section  of 
one  or  both  vagi.  But  the  disturbances  which  section 
of  the  vagus  sets  up  are  many.  One  of  them  is  a  very 
slow  breathing ;  and  it  was  found  that  when  artificial 
respiration  was  used  the  amount  of  bile  evacuated  by 
the  fistula  at  once  rose,  but  not  quite  to  the  normal 
amount.  If,  however,  only  one  vagus  be  divided,  it  is 
sometimes  long  before  the  slow  breathing  appears.  In 
two  cases  this  was  noted  ;  in  one  of  these  the  amount  of 
bile  was  unchanged  ;  in  the  other  it  sank  somewhat.  But 
little  can  be  inferred  from  these  experiments ;  and  it 
was  next  determined  to  divide  the  vagi  below  the  dia- 
phragm,   after   the   branches   to   the    lungs    had   been 

*  Edinburgh  Committee,  Report  of  the  Thirty -eighth  Meeting  of  the  British 
Association  for  the  Advancement  of  Science ;  held  at  Norwich  in  Aug.  1868.  Lond. 
1869,  p.  231. 

t  Schiff,  Canstatt's  Jahresbcricht  f.  1862,  Bd.  i.  p.  126,  quoted  from  Schwcizcr- 
schc  Zeitschriftf.  Heilkundc,  1862,  Bd.  i.  1862,  p.  i. 

}  Rohrig,  Stric]<er's  AJed.  Jalirbb,  1873,  p.  258. 


Diabetic  Puncture.  121 

given  off,  and  to  irritate  the  nerves  below  the  dia- 
phragm. In  making  the  bihary  fistula  a  ligature  was 
placed  on  the  gullet  below  the  diaphragm,  so  that  the 
vagi  could  readily  be  compressed.  The  amount  of 
bile  fell,  but  not  very  markedly.  Electrical  irritation  of 
the  vagi  was  followed  by  no  remarkable  increase  in  the 
amount  of  the  secretion  of  the  bile.  It  may  be  concluded 
that  the  vagi  have  no  immediate  influence  on  the  bile  ; 
but  the  changes  which  are  seen  are  due  to  slow  breath- 
ing, drawing  of  blood  from  the  liver  into  the  chest, 
decrease  of  movement  in  the  portal  system,  or  increase 
of  the  heart's  action,  all  of  which  tend  to  beget  a  passive 
congestion  of  the  liver.* 

Pfliiger,  without  giving  details,  shortly  reports  that 
he  has  cut  through  the  vagi,  phrenics,  splanchnics,  and 
sympathetics,  has  destroyed  the  cceliac  plexus,  has 
crushed  all  the  nerves  entering  the  porta,  and  yet  found 
the  secretion  of  the  bile  to  continue  as  before.  From 
this  he  draws  the  inference  that  the  liver  possesses  a 
nerve  centre  within  itself.  Irritation  of  the  vagi, 
splanchnics,  cceliac  plexus,  and  the  portal  nerves,  gave 
no  result.  If  the  liver  itself  be  irritated  with  electri- 
city for  one  or  two  minutes,  the  flow  of  bile  becomes 
very  slow,  or  even  leaves  ofl"  altogether,  for  as  much 
as  10  to  20  minutes.  Pfliiger  thinks  that  this  appear- 
ance cannot  be  explained  by  supposing  a  contraction 
of  the  vessels  or  bile  ducts. f 

Some  very  interesting  experiments  were  also  made  by 
Freundt  and  Graupe  in  Heidenhain's  laboratory  ;  they 
found  no  change  in  the  amount  of  fluid  bile  or  bile 
solids  after  the  diabetic  puncture  had  been  made  on  g 
guinea  pigs.  J 

*  Heidenhain,  Studien  d.  phys.Instituts  zu  Breslau,  Leipzig,  1863,  Heft.  ii.  p.  82. 

f  Pfliiger,  Arch.f.  d.  ges,  Phys.  i86g,  Bd.  ij.  p.  191.  Pfliiger  ends  his  paper 
with  the  words :  "  Bald  AusfiihrHcheres,"  but  I  do  not  know  of  any  paper  published 
afterwards  in  which  the  details  necessary  for  forming  a  judgment  on  the  results 
are  given. 

X  Heidenhain,  op.  cii.  p.  69. 


122  Effects  upon  the  Bile  of 

Heidenhain  and  his  pupils  found  that,  on  irritating 
the  spinal  chord  at  the  level  of  the  third  or  fourth  cervi- 
cal vertebrae,  the  amount  of  bile  was  decreased.  In 
the  one  experiment  given  to  us  as  a  specimen,  the  bile 
was  reduced  almost  one  half.  The  spinal  chord  was 
irritated  by  needles  inserted  into  the  neck,  along  which 
electricity  was  sent  by  means  of  a  magnet  electromotor. 
The  animal  showed  several  contractions  of  the  muscles 
during  the  time  of  irritation.  But  if  these  observa- 
tions be  looked  at  a  little  attentively,  it  is  seen  that 
there  were  two  periods  ;  one,  at  the  very  beginning  of 
the  irritation,  in  which  the  secretion  seemed  hastened  ; 
and  a  second,  following  the  first,  in  which  the  secre- 
tion was  decreased.  Casting  about  for  an  explanation 
of  these  two  appearances,  it  seemed  to  Heidenhain  that 
the  first  might  be  explained  by  supposing  an  increased 
flow  of  bile,  a  mere  driving  out  of  material  already 
formed ;  and  the  second,  by  supposing  a  narrowing 
of  the  intralobular  ducts,  which  would  thus  cause  a 
hindrance  to  the  descent  of  bile  formed.  Or,  as  the 
branches  of  the  mesenteric  and  hepatic  arteries  contract 
forcibly  when  the  spinal  chord  is  irritated,  it  might  be 
that  the  blood  pressure  in  the  capillaries  of  the  liver 
would  sink,  and  thus  a  true  decrease  of  the  secretion  of 
bile  take  place. 

In  deciding  between  these  two  hypotheses  it  must  be 
considered  that  if  there  be  a  narrowing  or  contraction  of 
the  gall  ducts,  there  would  be  no  tendency  of  fluid  to 
flow  back  into  the  liver,  when  a  tube  filled  with  fluid  is 
connected  with  the  common  duct,  and  the  tube  placed 
horizontally,  either  on  a  level  with  the  duct,  or  but 
slightly  above  it,  so  as  to  exert  but  small  pressure. 
During  the  first  period  of  irritation  of  the  spinal  chord, 
the  fluid  in  the  tube  remained  either  stationary,  or  was 
pushed  somewhat  forward.  During  the  second  period, 
the  fluid  ran  back  into  the  liver :    so  that  the  hypothe- 


Irritation  of  the  Spinal  Chord.  123 

sis  of  a  contraction  of  the  ducts  had  to  be  given  up. 
Now  this  flowing  back  of  the  bile  into  the  Hver  might 
be  due  to  three  things :  (i.)  a  decrease  of  secretion  ; 
(ii.)  an  increase  of  absorption  ;  or  (iii.)  a  combination 
of  both  these  circumstances.  The  bile,  however,  runs 
back  too  rapidly  for  the  appearance  to  be  due  solely  to 
a  decrease  of  the  secretion  only.  It  must  therefore  be 
an  increase  of  absorption.  To  what  is  this  increase 
of  absorption  due?  Heidenhain  answers:  to  a  de- 
crease of  the  blood  pressure  in  the  capillaries  of  the 
liver,  and  points  out  that  Frerichs  had  already  formu- 
lated such  a  theory  of  jaundice.*  Heidenhain  brings 
forward  experiments  made  by  his  own  pupils,  Kube  and 
Szostokowski,  which  show  that,  after  a  general  bleed- 
ing, the  bile  is  readily  absorbed  by  the  gall  ducts.  By 
again  injecting  blood  into  the  veins,  the  absorption 
becomes  less.  Max  Heidenhain  and  Lichtheim,  also, 
lowered  the  blood  pressure  in  the  liver  by  compressing 
the  aorta  in  rabbits  after  the  arteries  to  the  head  had 
been  given  off,  and  found  the  same  result.  With  com- 
pression, the  bile  was  absorbed  ;  during  the  intervals  of 
compression,  it  flowed  out  of  the  ducts. f  The  likeness 
of  the  states  caused  by  irritation  of  the  spinal  cord,  and 
by  mechanically  inducing  a  lowering  of  the  blood  pres- 
sure in  the  liver  is  thus  manifest.  The  contraction  of 
the  small  arteries  is  a  necessary  part  of  both.  Kube 
and  Szostakowski  have  also  made  experiments  in  which 
they  estimated  the  blood  pressure  in  the  carotid  at  the 
same  time  that  they  noted  the  changes  in  the  flow  of 
bile.  They  found  the  flow  of  bile  to  decrease  only 
when  a  great  increase  of  pressure  was  seen  in  the 
large  arteries  ;  that  is,  when  the  smaller  arteries  were 
contracted,  and  therefore,  the  pressure  in  the  capilla- 
ries was  small. 

*  Frerichs,  Klinik  d.  Leberkrankheiten,  Braunschweig,  1858,  Bd.  i.  p.  89-94. 
f  See  Ranke's  experiments  above,  p.  iig. 


124  Influence  upon  the  Bile  of 

The  appearance  of  an  increase  in  the  flow  of  bile, 
during  the  first  period  of  irritation  of  the  spinal  chord, 
Heidenhain  finds  it  more  difficult  to  explain.  He  falls 
back  upon  his  old  belief  in  a  contractility  of  the  gall 
ducts.  He  does  not  believe  that  there  is  any  increase  of 
secretion,  but  the  appearances  seen  in  his  experiments 
rather  suggest  that  the  secretion  already  formed  is  shot 
out  of  the  ducts  during  the  first  period.  Then  he  gives 
histological  reasons  for  thinking  that  the  gall  ducts 
contain  contractile  elements.*  Another  motive  is  the 
irregularity  of  the  appearance  of  the  secretion  which 
may  often  be  noted  in  animals  left  to  themselves. 
Heidenhain  ends  his  paper  by  the  notes  of  another 
experiment  on  compression  of  the  aorta  and  outflow  of 
bile.  The  flow  of  bile  was  great  during  the  time  of 
compression.  Heidenhain  sets  this  down  to  the  con- 
tractility of  the  gall  ducts,  because  the  muscular  coat 
of  the  bowels  and  the  uterus  contract  under  like  cir- 
cumstances.t 

Another  explanation  of  this  first  period  may  be  given. 
The  blood  vessels  and  gall  ducts  lie  close  together  in 
the  portal  spaces  in  the  liver.  Any  increase  in  the  one 
must  cause  a  decrease  in  the  size  of  the  other.  If,  be- 
fore the  contraction  of  the  small  arteries  begin,  there  be 
a  dilatation  of  them,  as  seems  quite  likely,  there  will  be 
a  pressure  exerted  upon  the  ducts  corrresponding  to 
the  dilatation  of  the  blood  vessels.  This  would  account 
at  once  for  the  apparent  increase  of  the  flow  of  bile, 
and  for  the  appearance  which  Heidenhain  has  noted 
that  it  was,  as  it  were,  shot  out  of  the  ducts. 

Rohrig  in  the  course  of  his  research,  made  an  at- 
tempt to  repeat  Heidenhain's  experiments  on  irritation 
of  the  spinal  chord.     He  did  not  use  the  same  method  of 

*  For  a  discussion  of  this  question  and  the  neighbouring  one  oi  icterus  spasticus, 
see  the  chapter  in  this  work  on  icterus  simplex. 

f  Heidenhain,  Studien  dcs  phys.  Instituts  zu  Breslau,  Leipzig,  1868,  Heft  iv. 
pp.  226-246. 


Irritation  of  the  spinal  Chord.  125 

irritation,  and  it  is  plain  therefore,  that  his  results  may 
not  be  compared  with  those  of  Heidenhain.  In  a  dog 
and  two  rabbits,  he  irritated  with  electricity  the  crural 
and  sciatic  nerves,  but  he  altogether  missed  the  first 
stage  of  increased  flow,  and  saw  only  the  second  stage, 
that  of  decreased  flow.* 

J.  Munk  has  repeated  these  experiments,  both  in 
Heidenhain's  way  and  in  Rohrig's  way,  and  comes  to 
the  conclusion  that  Heidenhain's  observations  are  right, 
and  that  Rohrig  is  mistaken. f 

Rohrig,  being  led  to  the  assumption  that  hypersemia 
of  the  bowels  and  liver  corresponded  to  an  increase  in  the 
activity  of  the  liver,  determined  to  watch  the  efl"ect  of 
cutting  the  splanchnic  nerves.  He  only  did  this  experi- 
ment  twice  ;  and  this  in  two  dogs  already  at  the  point  of 
death  from  other  experiments.  The  division  of  the 
nerves  was  followed  by  some  increase  in  the  amount 
of  bile,  but  ceased  in  a  few  seconds  with  the  life  of  the 
animal. J 

Munk  repeated  Rohrig's  experiment  of  dividing  the 
splanchnics  in  rabbits  ;  and  found  that  the  flow  of  bile 
was  first  hastened,  then  made  slower.  Assuming  that 
the  splanchnics  contain  the  greater  part  of  the  vaso- 
motor nerves  of  the  liver,  and  also  the  nerves  which, 
according  to  Heidenhain's  belief,  supply  the  muscular 
coat  of  the  gall  ducts,  it  would  follow  that  after  dividing 
the  splanchnics,  irritation  of  the  spinal  chord  would  not 
be  followed  by  any  change  in  the  flow  of  bile.  This 
assumption  was  verified  by  experiment.  Reflex  irrita- 
tion of  the  spinal  chord  of  a  rabbit  was  set  up  by  the 
irritation  of  the  sciatic  nerve  ;  and  as  a  consequence, 
first  a  quicker,  and  then  a  flow  of  bile  slower  than 
natural  took  place.    The  splanchnics  were  then  divided, 

*  Rohrig,  Strieker's  Med.  jfahrbb,  Wien,  1873,  p.  259. 
f  J.  Munk,  Arch.f.  d,  ges.  Phys.  1874,  Bd.  viii.  p.  151. 
X  Rohrig,  op.  cit,  pp.  257  and  258, 


126  Effects  of  Compression  of  Vessels 

and  the  sciatic  nerve  again  irritated,  but  no  change  in 
the  flow  of  bile  was  noted.* 

Rohrig  found  in  two  rabbits  that  division  of  the  spi- 
nal chord  high  up  in  the  neck  was  immediately  followed 
by  a  great  increase  of  the  flow  of  bile,  then  a  decrease, 
and  the  secretion  finally  ceased  with  the  death  of  the 
animal.  In  a  third  rabbit,  already  used  for  other  expe- 
riments of  compression  of  the  vessel,  this  method  of 
death  caused  a  slight  increase  in  the  flow.f 

Influence  of  the  ligature  of  certain  vessels. — The  effects 
of  Hgature  of  the  portal  vein  or  hepatic  artery  have 
already  been  discussed,  J  and  Heidenhain's  results  after 
compressing  or  tying  the  aorta  have  been  spoken  of.§ 

Rohrig  found  that  complete  ligature  of  the  aorta 
close  to  the  diaphragm  in  a  dog  and  a  rabbit  was 
followed  at  once  by  a  decrease  in  the  flow  of-  bile. 
Digital  compression  did  not  give  the  same  result. 
Ligature  of  the  aorta,  after  the  cceliac  had  been  given 
ofl",  caused  at  first  a  slight  increase  in  the  flow  of  bile 
which  became  weaker  and  weaker,  as  the  place  of  liga- 
ture was  moved  farther  down. 

The  same  observer  found  that  ligature,  complete  or 
incomplete,  of  the  vena  cava,  at  some  point  between 
the  left  auricle  and  the  hepatic  veins,  caused  a  decrease 
if  not  a  stoppage  of  the  flow  of  bile. 

Rohrig  comes  to  the  conclusion  that  the  secretion  of 
bile  is  not  altogether  dependent  on  the  blood  pressure 
in  the  liver.  The  blood  pressure  is  increased  when  the 
aorta  below  the  cceliac  is  tied,  and  yet  there  was  a  slight 
increase  in  the  flow  of  bile  ;  there  was  a  complete  stop- 
page of  the  flow  when  the  blood  pressure  was  raised  by 

•  J.  Munk,  Arch.f.  d.  gcs.  Phys.  1874,  Bd.  viii.  p.  160. 

f  Rohrig,  op.  cit.  p.  258.  The  results  of  Rohrig's  experiments  are  rendered 
much  less  valuable  from  a  scientific  point  of  view  by  his  custom  of  using  one 
animal  for  two  experiments. 

+  See  p.  87. 

§  See  p.  124. 


and  of  Irritation  of  Digestive  Canal.  127 

tying  the  inferior  cava.*  It  seems  to  me  that  the  two 
experiments  ought  not  to  be  compared. 

Effects  of  irritation  of  the  digestive  canal. — Rohrig  has 
irritated  the  mucous  membrane  of  the  mouth,  tongue 
and  stomach,  of  the  duodenum  and  large  and  small 
intestines,  the  peritonaeum,  by  means  of  ammonia  and 
acetic  acid,  and  weak  or  strong  electrical  currents,  and 
yet  seen  no  change  in  the  flow  of  bile.  In  a  few  experi- 
ments he  thought  that  dropping  a  little  ammonia  on 
the  tongue,  or  pinching  it  with  a  forceps,  called  forth  a 
momentary  increase.  He  has  never,  however,  seen  the 
least  change,  with  any  agent,  follow  irritation  of  the 
duodenum:  acetic  acid,  dilute  hydrochloric  or  sulphuric 
acid.f  It  should  be  remembered  that  Claude  Bernard 
noted  that  if  the  orifice  of  the  bile  duct  into  the 
duodenum  were  touched  with  weak  acetic  acid,  im- 
mediately a  rush  of  bile  poured  into  the  intestine. 
Nothing  of  the  sort,  however,  happened  if  instead 
of  acetic  acid,  a  slightly  alkaline  fluid  were  used,  as 
for  example,  carbonate  of  soda. J  Now  Tiedemann 
and  Gmelin  always  found  the  gall  bladder  empty  in 
animals  during  digestion,  and  they  explain  this  on  the 
theory  of  an  irritation  of  the  duodenum  by  the  chyme. 
No  doubt  they  are  right  in  this  view.  The  acid  chyme, 
passing  over  the  papilla,  causes  a  flow  of  bile  as  in 
Bernard's  experiment. 

Rohrig  injected  the  contents  of  the  stomach  and 
small  intestine  of  a  dog,  who  had  been  well  fed,  into 
the  stomach  of  another  dog.  There  was  a  much 
greater  increase  in  the  amount  of  bile  than  when  mere 
water  was  injected.     A  result  that  might  be  expected. 

.    *  Rohrig,  Strieker's  Med,  jfahrbb.  Wien,  1873,  p.  243. 

f  Rohrig,  ibid.  p.  248. 

J  Claude  Bernard,  Leqons  de  physiologie  experitnentale,  Paris,  1856,  t.  ij.  p.  429. 
This  experiment  has  been  repeated  and  confirmed  by  Kiithe  {Ziir  Function  der  Leber, 
in  Heynsius'  Studien  des.  pliys.  Inst.  211  Amsterdam,  Leipzig  and  Heidelberg,  1861,  p. 
38.)     Of.  Tiedemannn  and  Gmelin,  Recherches,  etc.     Paris,  1827,  partie  i.  p.  375. 


128  Pressure  under  which  Bile  is  Secreted. 

He  found  that  during  diarrhoea  the  flow  of  bile  was 
very  abundant.*  The  exposure  of  the  intestines  to  the 
air  was  also  followed  by  some  increase  of  the  secretion. 

H.  Nasse,  however,  had  noted  in  1847  ^^^^  i^  diar- 
rhoea the  amount  of  bile  was  decreased, t  and  the  Edin- 
burgh Committee, J  in  1868,  and  Dr.  Rutherford  later 
on,  after  Rohrig's  experiments,  did  not  find  that  active 
purging  increased  the  secretion  of  bile.  "Whether  or 
not,"  says  Dr.  Rutherford,  "the  depressing  effect  on  the 
liver  is  due  to  the  tendency  towards  collapse  that  results 
from  violent  purgation,  or  to  the  abundant  abstraction 
of  certain  matters  from  the  portal  vein,  is  doubtful. 
The  point,  however,  is  one  of  such  importance  that  it 
demands  further  investigation. §" 

In  disease. — H.  Nasse  noted  that  if  his  dog  became 
feverish,  the  amount  of  bile  was  decreased. || 
■  Pressvtre  under  which  the  bile  is  secreted. — Heidenhain, 
and  his  pupils,  Friedlander  and  Barisch,  found  that 
when  a  manometer  was  connected  with  the  gall  bladder 
of  a  guinea  pig,  in  whom  a  biliary  fistula  had  been 
made,  the  bile  or  water  of  the  manometer  rarely  rose 
above  200  millimeters  in  height.  After  reaching  this 
height  it  remained  tolerably  constant.  The  bile  is 
therefore  secreted  at  the  small  pressure  of  200  mm. 
of  water  pressure.^  Kowalewsky  finds  that  in  woorar- 
ised  cats,  the  pressure  is  not  constant,  but  liable  to 
variations,  from  12  to  20  mm.  of  mercury.  These  vari- 
ations depend  chiefly  upon  the  variations  in  the  arterial 


•  Rohrig,  Strecker's  Med.  Jahrb.  Wien,  1873,  p.  248. 

f  H.  Nasse,  Covimentatio  de  bills  quotldlc,  etc.  p.  19. 

X  Edinburgh  Committee,  Report  of  the  Thirty-eighth  Meeting  of  the  British 
Association  for  the  Advancement  of  Science ;  held  at  Norwich,  August,  1868,  Lond. 
1869,  p.  229. 

§  Rutherford  and  Vignal,  Experiments  on  the  Biliary  Secretion  of  the  Dog,  p. 
17:  Report  attached  to  the  Brit.  Med.  jfournal,  Vol.  ii.  1876. 

II  H.  Nasse,  Commcntatlo  de  bills  quotldlc,  etc.  Marburg,  1851,  p.  19. 

U  Friedlander  and  Barisch,  Arch.f.  Anat.  Phys.  1S60,  p.  659. 


Summary  of  Knowledge.  129 

pressure.  The  pressure  under  which  the  bile  is  secreted 
rises  with  the  rise  of  the  blood  pressure.  The  change 
is  not  immediate,  but  needs  some  time  before  it  be 
brought  about,  due  doubtless  to  some  changes  going 
on  either  in  the  secretion  of  the  bile  or  absorption  from 
the  ducts.  The  resistance  to  the  passage  of  the  bile 
into  the  bowel  also  varies  in  the  same  species.  For  ex- 
ample, in  woorarised  cats  it  varies  from  3*4  to  7*5  mm. 
of  mercury.  The  bile  will  thus  be  stopped  entering  the 
duodenum  if  a  resistance  of  only  3*4  to  7*5  mm.  of  mer- 
cury be  opposed  to  it.* 

Summary  of  Knowledge  as  to  the  Physiology  of  the  Bile. 
It  is  much  to  be  regretted  that  the  physiology  of  the 
bile  is  still  in  so  unsatisfactory  a  state.  Compared 
with  it,  the  chemistry  of  this  humour  might  almost  be 
looked  upon  as  a  well-worked  field,  although  physio- 
logical chemistry  has  made  but  small  progress  in  what 
may  really  be  called  knowledge. 

It  is  still  uncertain  if  the  liver  be  a  mere  filter,  or  if  it 
secrete  the  bile  itself,  although  the  general  belief  of 
physiologists  is  in  favour  of  the  latter. 

Of  late  years  a  belief  in  a  kind  of  circulation  of  the 
bile  has  much  prevailed  ;  that  is,  that  the  bile  is  secreted 
by  the  liver,  passed  into  the  intestines,  absorbed  by  the 
intestines,  passed  into  the  blood,  and  again  brought  back 
by  the  blood  to  the  liver  to  be  again  excreted. 

It  is  also  thought  that  the  bile  pigments  are  direct 
derivatives  of  the  haemoglobin  of  the  blood  corpuscles, 
though  the  evidence  in  favour  of  this  has  of  late  become 
weaker.  The  bile  acids  must  be  derived  from  some 
nitrogenous  bodies,  and  it  is  therefore  probable  enough 
that  they  come  from  the  albuminous  compounds  of 
the  system,  though  whether  the  breaking  down  of 
the  tissues  or  the  splitting  up  of  the  peptones  from  the 

*  Kowalewsky,  Anh.f,  d.  ges.  Phys,  1S74,  Bd.  viij.  p.  597. 

K 


130  Summary  of  Knowledge  as 

food  furnish  the  bile  acids  is  not  known.  It  is  doubtful 
if  the  cholestearin  and  lecithin  be  formed  in  the  liver  or 
are  merely  excreted  from  the  blood.  It  would  appear 
that  a  supply  of  blood  from  the  hepatic  artery  is  needful 
for  the  secretion  of  bile,  as,  if  arterial  blood  be  com- 
pletely kept  out  of  the  liver,  death  of  the  liver  takes 
place  ;  but  whether  the  portal  vein  only  bring  the  ma- 
terials of  the  bile  is  not  known. 

The  amount  of  bile  both  in  man  and  brutes  secreted 
during  the  24  hours  is  liable  to  very  considerable  fluc- 
tuations in  health.  In  the  few  cases  in  which  biliary 
fistulae  have  been  established  in  man,  and  the  amount  of 
bile  estimated  with  care,  the  bile  has  varied  from  7  to 
22  ounces  in  the  24  hours.  In  the  two  instances  in 
which  the  calculation  has  been  made  in  man,  one  kilo- 
gramme has  secreted  7*34  grm.  and  14  grm.  of  fluid 
bile,  and  0'i66  grm.  and  0*44  grm.  of  solid  bile  in  the 
24  hours.  A  glance  at  the  table  given  by  the  Edin- 
burgh Committee  (see  p.  104.)  will  show  how  much 
greater  are  the  variations  in  dogs. 

It  would  seem  likely  that  the  taking  of  food  into  the 
stomach  is  followed  in  an  hour  or  two  by  an  increased 
secretion  of  bile.  In  man,  it  seems  doubtful  if  this  be 
always  the  case.  Perhaps  this  may  be  explained  by 
the  frequency  with  which  meals  are  taken  by  man,  by 
which  the  liver  is  being  continually  excited,  and  so  feels 
less  the  stimulus  of  any  one  meal  ;  while  in  dogs,  which 
nature  intended  should  be  fed  only  once  in  the  day,  or 
less  often  than  this,  the  liver  feels  the  ingestion  of  a 
meal  as  a  rare  excitement. 

During  fasting  the  amount  of  bile  is  much  decreased. 

No  definite  relation  has  yet  been  discovered  between 
the  kind  and  amount  of  food,  and  the  amount  of  bile. 

During  the  night,  especially  after  midnight,  a  less 
amount  of  bile  is  secreted  ;  but  it  is  more  concentrated. 
Observers  are  much  at  variance  whether  drink  increase 


to  the  Physiology  of  the  Bile.  131 

the  amount  of  a  diluted  bile,  as  with  the  urine,  or 
whether  it  have  no  influence  on  the  bile,  or  whether 
the  bile  be  decreased  in  amount.  Some  think  that  a 
greater  amount  of  a  highly  pigmented  bile  follows  the 
injection  of  water  into  the  veins. 

No  nervous  influence  has  yet  been  found  directly  to 
aff"ect  the  secretion  of  bile.  The  diabetic  puncture  is 
followed  by  no  change. 

On  lowering  or  raising  the  blood  pressure  in  the 
liver,  the  amount  of  bile  which  escapes  from  a  biliary 
fistula  is  decreased.  It  is  probable  that  the  decrease  of 
bile  seen  during  a  low  blood-pressure  is  due  to  the 
passing  of  the  bile,  already  secreted,  into  the  blood,  and 
is  not  due  to  a  real  decrease  of  secretion. 

Purging  causes  a  decrease  in  the  amount  of  bile 
secreted. 

The  bile  is  secreted  in  guinea-pigs  and  in  cats  at  a 
very  low  pressure. 

Irritation  of  the  papilla  in  the  duodenum,  by  an  acid, 
is  followed  by  a  rush  of  bile  into  the  duodenum.  The 
acid  chyme  is  therefore  probably  the  natural  irritant  of 
the  gall-bladder  and  ducts. 

Vomiting  is  followed  by  an  increased  expulsion  of 
bile  ;  so  also  is  muscular  exercise. 


K  2 


CHAPTER   VII. 

The  Office  of  the  Bile. 

It  would  seem  necessary  that  a  secretion,  which  is 
mixed  with  the  food  almost  as  soon  as  it  leaves  the 
stomach,*  which  is  the  product  of  the  largest  gland  in 
the  body,  a  secretion  in  the  dog  said  to  equal,  in  24  hours, 
■g'o  of  his  weight  and  of  a  rabbit  ^,  should  have  some 
notable  purpose  in  the  animal  ceconomy.  Yet  physio- 
logists have  striven,  and  probably  will  strive,  for  many 
years  over  the  uses  of  the  bile.  The  same  obscurity 
which  hangs  over  the  rest  of  the  physiology  of  this 
humour  envelopes  to  an  equal,  if  not  a  greater,  degree, 
the  use  to  which  it  is  designed  by  nature. 

Is  the  bile  an  excrement  only  or  not  ?  It  was  taught  by 
Aristotle  that  in  animals  the  gall  was  an  excrement 
and  served  no  special  purpose. "j*  It  is  said  also  that 
Paracelsus  considered  the  bile  a  useless  humour  and 
superfluous  member  of  the  animal  ceconomy. J  In 
modern  times  the  doctrine  of  Aristotle  has  been  main- 
tained, but  not  wholly,  by  Tiedemann  and  Gmelin,§ 
before  Blondlot. 

It  might  be  thought  this  question  of  the  excremental 
character  of  the  bile  would  be  settled  by  diverting  the 
natural  course  of  the  bile  from  the  intestine  to  the  out- 
side of  the  body.      This  was  done  by  Schwann,  who 

*  In  omnibus  animalibiis  bills  in  principium  intestini  adfunditur,  ut  nihil  fere 
alimenti  ad  sanguinem  veniat,  quod  cum  ea  non  mistum  sit.  (Haller,  Elcm.  Phys. 
Lugd.  Bat.  1764,  t.  vj.  p.  615.) 

f  Aristotle,  On  the  parts  of  animals,  Book  iv.  Chapter  ij.  Taylor's  ed.  Lond. 
1810,  p.  113. 

X  Paracelsus,  quoted  by  Eisenmann,  Die  Kyankhcils-Fnmilic  Cholosis,  Erlangen, 
1836,  p.  13. 

§  Tiedemann  and  Gmelin,  Recherches  ^c.  say  la  Digestion,  Paris,  1827,  2e 
Partie,  p.  58. 


If  only  an  Excrement.  133 

devised  a  method  of  making  such  bihary  fistulse.  His 
results  were  these  :  out  of  18  dogs  the  common  duct  was 
re-estabhshed  in  2,  and  in  10  death  might  be  looked 
upon  as  the  result  of  the  operation.  So  that  only  six 
remain.  They  died  in  7,  13,  17,  25,  64,  and  80  days 
after  the  operation,  with  symptoms  of  inanition,  loss 
of  flesh,  muscular  weakness,  unsteadiness  of  gait,  and 
falling  out  of  the  hair.  These  symptoms  were  the  more 
pronounced,  the  longer  the  animal  lived.  No  dif- 
ference was  seen  if  the  creature  licked  up  the  bile 
from  the  fistula,  or  if  it  were  hindered  from  so  doing. 
Schwann  believes  that  the  bile  is  not  solely  an  excre- 
ment like  the  urine,  but  is  essential  to  life  ;  that,  if  it  be 
diverted  from  the  intestine,  a  loss  of  weight  at  once  sets 
in,  and  that  death  will  follow  in  2.  or  3.  weeks,  some- 
times more,  sometimes  less.* 

Blondlot,  on  the  other  hand,  set  up  a  biliary  fistula 
in  a  dog ;  and  after  the  first  week  or  two,  during  which 
the  animal  was  out  of  health,  as  it  licked  the  bile  from 
the  wound,  the  dog  regained  its  former  state  and  its 
usual  amount  of  fat.  It  ran  about  the  house,  and  went  for 
walks  in  the  town  and  country,  appearing  to  ail  nothing. 
Blondlot  concludes  from  this  one  experiment  that  the 
bile  is  of  no  use,  but  is  simply  an  excrement. f  Schwann 
later  on  repeated  his  experiments  on  thirty  dogs.  In 
the  end,  all  died  ;  but  one  lived  a  year,  and  another 
four  months.  Nasse  kept  a  dog  alive,  with  the  weight 
tolerably  the  same,  from  the  12th  of  August  in  one  year, 
to  the  27th  of  January  in  the  next.  J  The  Edinburgh 
Committee  kept  in  good  health  a  dog  with  a  biliary  fistula 

*  Schwann,  Arch.f.  Anat.  Phys.  ti.s.w.  1844,  p.  127. 

f  Blondlot,  Essai  stir  les  Fonctions  du  foie,  Paris  and  Nancy,  1846,  pp.  55  et 
scqq.  This  dog  of  Blondlot's  lived  five  years  in  perfect  health,  was  active,  used 
for  hunting,  and  had  pups  every  year.  It  died  without  apparent  cause,  and  on  dis- 
section the  obstruction  of  the  ducts  was  found  to  be  perfect.  (See  Comptes  rendus, 
1851,  t.  xxxii.  p.  904.) 

X  Schwann  and  Nasse,  quoted  by  Frerichs,  Wagner's  Handwortcrbuch  d.  Phy. 
siologie,  Braunschweig,  1846,  Bd.  iii.  Abth.  i.  p.  837. 


134  ^f  ^'^h  ^^  Excrement 

from  April  24,  1868,  to  September  11  of  the  same  year. 
It  gained  nearly  4  kilogrammes  in  weight  during  the  five 
months  that  it  lived  without  bile  passing  into  the  intes- 
tine ;  and  had  kept  its  strength,  notwithstanding  a  par- 
tial poisoning  with  corrosive  sublimate,  purging  with 
podophyllin,  and  dosing  with  taraxacum.*  The  Com- 
mittee think  that  much  depends  on  the  health  of  the 
animal  at  the  time  that  the  biliary  fistula  is  established. 
If  the  strength  be  good,  health  is  usually  preserved. 

The  observations  of  Bidder  and  Schmidt  confirmed 
in  all  the  more  important  particulars  the  results  of 
Schwann.  In  their  first  experiment  they  found  the 
dog  to  lose  weight  daily,  although  he  was  fed  with  four 
hundred  grammes  (nearly  half  a  pound)  of  meat.  His 
weight  before  the  operation  was  six  kilogrammes  ;  after 
death  at  the  end  of  a  month,  less  than  three  and  a  half. 
Thus,  the  wasting  of  the  animal  was  something  very 
noteworthy.  The  skin  was  loose,  the  muscles  scarcely 
to  be  felt,  and  the  movements  of  the  animal  were  very 
weak,  although  it  was  only  on  the  day  before  its  death 
that  it  did  not  leave  its  kennel.  The  hairs  fell  out  in 
great  abundance,  leaving  bald  spots  on  the  trunk  and 
limbs.  A  great  contrast  to  the  miserable  appearance, 
was  the  enormous  appetite,  of  the  creature.  Digestion 
seemed  to  go  on  much  as  usual.  The  stools  were 
not  frequent,  but  were  remarkable  for  their  filthy 
smell  ;  so  also  was  the  flatus  which  was  passed  by  the 
animal  almost  incessantly.  Much  the  same  appear- 
ances were  seen  in  their  second  experiment.  In  their 
third,  the  spleen  was  first  removed  and  then  a  fistula 
set  up.  The  dog  lived  two  months  and  was  killed.  It 
showed  the  same  great  appetite,  loss  of  flesh,  and  other 
symptoms  that  the  others  did  ;  only  it  seemed  to  pre- 
serve its  health. 

•  Edinburgh  Committee,  Report  of  the  Thirty-eighth  Meeting  of  the  British 
Association  for  the  Advancement  of  Science ;  held  at  Norwich  in  August,  1868, 
London,  1869,  p.  231, 


or  Needful  for  Digestion.  135 

Bidder  and  Schmidt  conclude  that  the  question 
whether  the  bile  be  merely  an  excretion  cannot  be 
answered  simply  with  yes  or  no.*  In  some  cases  it 
may  be  looked  on  as  such,  when  the  drain  caused  by 
the  loss  of  bile  can  be  fully  covered  by  the  increased 
amount  of  food  taken  ;  but  in  the  greater  number  this 
compensation  is  not  possible,  and  the  loss  becomes  so 
great  that  life  can  no  longer  be  kept  up. 

Is  the  bile  needful  for  digestion  in  the  stomach  and 
intestines  ?  Eaglesfield  Smith  found  some  advantage 
to  the  digestion  in  a  case  of  jaundice  in  administering 
the  bile  of  mammals.  In  Abyssinia  and  other  uncivil- 
ised countries,  he  says,  bile  is  thought  to  be  a  stomachic 
and  a  luxury  ;t  he  immersed  flesh  in  gall  for  14  hours 
at  a  heat  equal  to  the  human  body,  and  found  that  it  had 
lost  half  its  weight ;  and  he  thinks  therefore  that  bile 
is  of  great  aid  in  digestion,  due  to  its  power  of  acting 
on  grease. J 

In  order  to  test  this  theory  that  the  bile  aided  the 
formation  of  chyle,  the  first  Sir  Benjamin  Brodie  con- 
ceived the  idea  of  tying  the  bile  duct,  and  thus  hinder- 
ing the  bile  from  passing  into  the  intestine.  He  then 
watched  the  effect  on  the  digestion.  That  in  the 
stomach  he  found  to  continue  as  usual ;  but  the  con- 
version of  chyme  into  chyle  was  invariably  and  com- 
pletely interrupted  :  not  the  smallest  trace  of  chyle  was 
perceptible  either  in  the  intestines  or  in  the  lacteals.§ 

Magendie  repeated  Brodie's  experiments  in  two 
animals,  and  found  that  white  chyle  was  formed, 
together  with   faeces  which   resembled    ordinary  fasces 

*  Bidder  and  Schmidt,  Die  Vcrdauungssaefte,  Mitau  and  Leipzig,  1852,  pp. 
98-114. 

f  Dr.  George  Harley  says  that  bile  is  drunk  with  great  glee  by  the  Kaffres. 
[yaundice,  London,  1S63,  p.  18.) 

X  Eaglesfield  Smith,  Etiropemi  Magazine,  1797,  Vol.  xxxi.  p.  386.  Cf.  Observa- 
tions and  experiments  on  the  digestive  powers  of  the  bile  in  animals.  Lend.  1805. 

§  Brodie,  Quarterly  yournal  of  Science,  1823,  Vol.  xiv.  p.  342, 


136  Bile  not  Needful  for 

save  that  they  were  white.*  Tiedemann  and  Gmelin, 
however,  found  that  while  the  Hquid  in  the  lacteals  of 
dogs  whose  bile  ducts  had  not  been  tied  was  whitish,  it 
was  without  colour  and  clear  in  those  in  whom  they  had 
been  tied  ;  so  also  was  the  fluid  in  the  thoracic  duct.  The 
difference  is  due  to  the  absence  of  fatty  particles  which 
give  a  milky  appearance  to  the  fluid.  The  formation 
of  chyle  was  not  absolutely  put  an  end  to,  as  Brodie 
maintains,  but  that  less  fat  was  absorbed  when  the  bile 
was  hindered  from  passing  into  the  duodenum. f 

Bidder  and  Schmidt  examined  the  chyle  from  the 
thoracic  duct  of  dogs  with  biliary  fistulse  ;  in  no  case 
did  they  find  it  white,  but  opalescent,  transparent,  now 
and  then  yellowish  ;  it  clotted  as  soon  as  taken  from 
the  duct.  Of  three  cases,  there  were  55*26,  58*42, 
and  83*38  j5>ro  mille  of  solids,  figures  which  are  within 
the  averages  of  health.  The  amount  of  fat  in  the 
chyle  was,  however,  very  small.  The  amount  with 
ordinary  nourishment  in  a  healthy  dog  may  be  as  high 
as  32  pro  mille.     In  these  it  was  under  2  pro  mille. 

Bidder  and  Schmidt  also  examined  the  faeces  of  ani- 
mals in  whom  the  bile  was  cut  off  from  the  intestine. 
They  found  that  the  albuminous  bodies  of  the  food  had 
almost  entirely  disappeared  from  the  faeces ;  so  also 
had  the  starch,  while  a  good  part  of  the  fats  was 
also  absorbed  ;  one  kilogramme  of  the  animal  taking 
5*17  grm.  of  fat  in  the  24  hours.  J  Some  part  of  the 
fat  which  is  ordinarily  absorbed  is  therefore  not  taken 
up  when  bile  is  not  present. 

Certain  Chemical  Properties  of  the  Bile.  These  pro- 
perties should  have  been  discussed  under  the  chapter 
on  the  chemistry  of  the  bile  ;  but  it  is  more  convenient 

*  Magendie,  Precis  Hem.  dc  phys.  Paris,  1836,  46  ed.  t.  ij.  p.  iig,  note, 
f  Tiedemann  and  Gmelin,  Rcclicrches  cxf>.  etc.  sur  la  Digestion,  Paris,  1827, 
2e  Partie,  pp.  55  and  95. 

I  Bidder  and   Schmidt,  Die   Verdauungssaeftc,  Mitau   and  Leipzig,   1852,  pp. 

270-228. 


the  Forming  of  Chyle.  137 

to  consider  them  at  this  point  with  the  use  of  the   bile 
in  the  digestion  of  aHments. 

That  bile  has  some  power  of  emulsifying  fats  is 
well  known  from  its  domestic  use.  When  shaken 
up  with  oil  it  forms  an  emulsion  better  than  plain 
water,  but  not  nearly  so  well  as  pancreatic  juice. 
Dr.  Bence  Jones  says  that  bile  has  no  chemical 
action  whatever  on  the  neutral  fats.*  And  in  this 
Lenzf  and  others  agree  with  him.  Lenz  says  that  if 
ox  bile  be  mixed  with  an  equal  quantity  of  pure  oleic 
acid,  shaken  together,  and  the  whole  kept  at  a  tempera- 
ture of  35°  to  40°  C.  (95°  to  104°  F.)  then  three  layers 
are  formed  ;  the  uppermost  contains  pure  oleic  acid  ; 
the  lowest  pure  bile  ;  while  the  middle  is  of  a  whitish 
green  colour  and  soluble  in  water.  This  can  be  again 
divided  by  hydrochloric  acid  into  two  layers,  one  of  pure 
oleic  acid,  the  other  of  chloride  of  sodium.  So  that 
it  is  the  soda  salts  of  the  bile  which  form  a  soap  with  the 
fatty  acids.  Free  fatty  acids  maybe  formed  by  the 
action  of  the  pancreatic  juice.  But  the  greater  part  of 
the  fat  of  the  chyle  is  not  soap,  but  finely-divided  fat  in 
minute  drops  and  granules. 

C.  A.  von  Wistinghausen  found  that  oil  passed  more 
readily  through  animal  membranes  moistened  with  bile 
than  with  water  ;  and  more  readily  at  the  temperature  of 
the  body  than  at  a  temperature  of  19°  C.  Also  that  oil  rose 
more  readily  in  capillary  tubes  wetted  with  bile  than  in 
tubes  that  were  dry  or  wetted  with  water.  J 

Mr.  Charles  H.  Williams  has  also  made  some  careful 
investigations    on   this  point   in    Professor    Bowditch's 

*  Bence  Jones,  Medical  Times,  1851,  July  5,  p.  3. 

f  Lenz,  de  adipis  concoctione  ct  absorptione,  diss,  inaug.  Dorpati,  1850,  quoted 
by  Bidder  and  Schmidt,  op.  cit.  p.  228. 

%  C.  A.  von  Wistinghausen,  Experimenta  quaedam  endosmotica  de  bills  in 
absorptione  adipuni  nentralimn  partibus,  Diss.  Inaug.  Dorpati  Livonorum,  1851. 
This  tract,  which  had  been  almost  forgotten  by  physiologists,  has  been  reprinted 
in  substance  by  J.  Steiner,  in  Archiv  f.  Anat.  Phys.  u.s.w.  1873,  p.  137. 


138  Bile  turns  Starch  into  Sugar 

laboratory  In  the  Harvard  Medical  School.  He  finds 
that  oils  pass  more  readily  through  membrane  or  plas- 
ter wet  with  bile  than  through  membrane  or  plaster  wet 
with  water.  This  is  increased  if  the  bile  be  alkaline 
and  decreased  if  it  be  acid. 

He  concludes  that  the  action  cannot  be  due  to  the 
bile  changing  the  form  of  the  pores  ;  and  he  finds  also 
that  after  passing  through  membranes  moistened  with 
bile,  the  fats  appear  more  finely  divided  than  when 
passed  through  membranes  wet  with  other  fluids  ;  and 
he  infers  that  the  drop-tension  or  cohesion  of  the  fat 
has  been  affected.* 

Thirty  years  ago  it  was  denied  that  bile  had  the 
property  of  turning  starch  into  sugar ;  but  von  Wittich 
has  shown  that  this  office  is  enjoyed  by  fresh  human 
bile  as  well  as  that  of  many  animals. t  Bufalini  has  of 
late  confirmed  this  observation  of  von  Wittich's,  and 
further  finds  that  fresh  bile  has  also  the  property  of 
changing  the  hepatic  glycogen  into  sugar.  When  bile 
is  deprived  of  its  mucus  and  pigments  by  means  of  slight 
acidulation  with  acetic  acid  and  animal  charcoal,  it  still 
retains  this  power ;  but  the  change  is  longer  in  being 
accomplished,  probably  because  some  of  the  ferment  is 
carried  away  with  the  mucus.  Putrefying  bile  does  not 
change  starch  or  glycogen  into  sugar  ;  nor  do  the  bile 
acid  salts. J 

Upon  the  sugars  themselves  bile  appears  to  have 
no  more  action  than  other  animal  matters  have. 
Thus  it  forms  lactic  acid  if  kept  for  a  long  time  with 


*  Charles  H.  Williams,  Experiments  on  the  action  of  Bile  in  promoting  the 
absorption  of  Fats,  Prize  Essay  of  the  Boylston  Medical  Society  for  1874,  pub- 
lished as  Supplement  to  the  ninetieth  volume  of  the  Boston  Medical  and  Surgical 
yournal. 

f  von  Wittich,  Arch.f.  d.  ges.  Phys.  1872,  Bd.  vj.  p.  182.  H.  Hoffman  (Haser's 
Archiv  1844,  Bd.  vj.  p.  157,  Bericht  in  Arch.f.  Anctt.  Phys.  u.s.w.  1846,  p.  27)  dis- 
tinctly says  that  bile  can  turn  starch  (Kleister)  into  dextrin  and  sugar. 

X  Bufalini,  Lo  Spcrimcntale,  abstract  in  London  Medical  Record,  1879,  p.  149. 


but  Dissolves  no  Albumen.  139 

grape  sugar  or  cane  sugar.*  It  was  once  thought  that 
bile  could  turn  sugar  into  fat  ;t  a  notion  refuted  by  the 
experiments  of  Schiel,J  and  Frerichs.§ 

Bile  has  no  solvent  action  on  the  albumens.  Hiine- 
feld  noticed  that  the  bile  dissolved  the  red  blood  cor- 
pusclesll  and  this  property  was  extended  to  the  more 
important  articles  of  diet,  so  that  Platner  allowed  a 
certain  small  power  in  bile  to  dissolve  loosely-clotted 
albumen,  fibrin,  and  casein.^  The  experiments  of  von 
Gorup-Besanez**  showed  that  bile  had  no  influence  on 
white  of  &gg,  boiled  or  fresh  beef,  but  seemed  to  favour 
the  idea  that  cheese  was  dissolved  by  bile.  This  has 
been    disproved   by   the    experiments    of    Bidder    and 

Schmidt.tt 

A  strange  view  of  the  office  of  the  bile  was  enter- 
tained by  Prout.  "  If  the  food  originally  contained  no 
albuminous  matter ;  no  albumen  is  developed  in  the 
stomach  ;  but  immediately  on  the  entrance  of  the  semi- 
fluid mass  into  the  duodenum,  and  its  mixture  with  the 
bile  and  the  pancreatic  fluids ;  albuminous  and  other 
chylous  matters,  become  distinctly  perceptible."  Later 
on  he  says  that  some  of  the  albumen  may  be  developed 
from  the  pancreatic  fluid,  but  the  whole  is  too  great  to 
be  explained  in  this  manner.JJ 

It  was  known  early  in  this   century  that  the  chyme 

*  Bence  Jones,  Medical  Times,  1851,  July  5,  p.  3.  This  is  probably  copied  from 
Frerichs,  who  says  the  same  thing.  (Wagner's  Handworterbtich  d.  Physiologie, 
Branschweig,  1846,  Bd.  iii.  Abth.  i.  p.  835.) 

f  Henr.  Meckel  ab  Hemsbach  de  gcnesi  adipis  in  animalibus  Diss,  inaug.  med. 
Halis  ;  quoted  in  Canstatt's  Jahresb.f.  1845,  Bd.  i.  p.  143. 

X  Schiel,  Zeitschriftf.  rat.  Med.  1846,  Bd.  iv.  p.  375. 

§  Frerichs,  loc,  cit. 

II  Hiinefeld,  Der  Chemisnms  in  der  thierischen  Organisation,  Leipzig,  1840,  p. 
102. 

IT  Platner,  Ueber  die  Natur  u.d.  Nutzen  d.  Galle,  Heidelberg,  1845,  p.  124. 

**  E.  von  Gorup-Besanez,  Untersuchungen  ueber  Galle,  Erlangen,  1846,  p.  46. 

f-f  Bidder  and  Schmidt,  op,  cit.  p.  219. 

XX  Prout,  Chemistry,  Meteorology,  and  the  Function  of  Digestion  considered  with 
reference  to  natural  Theology,  Bridgewater  Treatise,  London,  1834,  p.  508. 


140  Precipitation  of  Peptones 

was  thrown  down  when  brought  into  contact  with  bile.* 
It  was  also  demonstrated  by  Eberlef  and  insisted  on  by 
nearly  every  physiologist  after  him.  Platner  apparently 
believed  that  the  precipitate  was  a  combination  of  the 
bile  acids  with  albumen  or  pepsin. J  He  stated  that 
the  combination  of  bile  acids  and  albumen  could  hardly 
be  digested  even  if  kept  for  days  with  artificial  gastric 
juice. 

It  was  very  distinctly  taught  by  Claude  Bernard  that 
if  bile  be  added  to  the  gastric  juice,  the  work  of  di- 
gestion is  at  once  arrested.  If  meat  be  kept  in  gastric 
juice  at  the  proper  temperature,  the  particles  of  the 
muscular  fibres  are  broken  up,  and  this  is  the  pecu- 
liar office  of  the  gastric  juice.  But  if  bile  be  added, 
the  process  ceases  at  once.  The  presence  of  bile  in 
the  stomach  puts  an  end  to  digestion.  Even  if  the 
gastric  juice  remain  acid,  it  loses  its  digestive  properties. 

When  the  albuminous  bodies  which  have  been  dissolved 
by  the  gastric  juice  arrive  in  the  duodenum,  they  are  at 
once  thrown  down  by  the  bile  ;  but  the  bodies  free  from 
nitrogen  remain  untouched.  No  precipitate  is  formed 
if  bile  be  added  to  the  gastric  juice  from  a  fasting 
animal,  or  from  one  which  has  eaten  only  fat,  starch, 
or  sugar.  But  when  the  nitrogenous  elements  of  the 
food  pass  through  the  pylorus,  a  yellow  precipitate  is 
thrown  down  of  everything  dissolved,  and  this  preci- 
pitate adheres  to  the  walls  of  the  gut.  The  viscid 
secretion  of  the  duodenal  glands  helps  to  entangle  the 
precipitate,  and  to  keep  it  in  the  duodenum,  to  under* 
go  for  a  longer  time  the  action  of  the  digestive  fluids. 

By  the  precipitation  of  the  chyme  by  the  bile,  the 
activity   of  the   gastric  juice   is  wholly  brought   to   an 

•  Autenrieth,  Handbuch  d.  emp.  mensch.  Physiologie,  Tiib.  1802.  Bd.  ij.  p.  98. 
Werner,  quoted  by  Eberle,  Physiologie  der  Vcrdauiing,  Wiirzburg,  1834.  p.  210. 
Blundell,  1817,  quoted  by  Elliotson,  Human  Physiology,  London,  1840.  p.  ioi,note. 

f  Eberle,  Physiologic  d.  Vcrdmiung,  Wiirzburg,  1834,  p.  igo. 

X  Platner,  Ucber  die  Natnv  iind  den  Nutzcn  der  Galle,  Heidelberg,  1845,  P-  ^26. 


by  the  Addition  of  Bile.  141 

end.     If  the  chyme  be  filtered,  the  filtrate  has  no  longer 
any  digestive  power.* 

That  the  gastric  juice  holding  peptones  in  solution  is 
thrown  down,  and  rendered  inactive,  by  the  addition  of 
bile,  is  assented  to  by  nearly  every  physiologist.  Dr. 
Dalton,  however,  says  that  he  has  invariably  found  that 
if  the  gastric  juice  be  digested  with  white  of  &gg,  the 
filtered  fluid  will  no  longer  give  the  slightest  precipitate 
on  the  addition  of  bile. f 

According  to  Claude  Bernard,  the  precipitate  thrown 
down  by  the  bile  from  the  chyme  is  redissolved  by  the 
pancreatic  juice.  Also  if  pieces  of  the  food,  such  as 
casein  or  flesh,  not  yet  entirely  dissolved  by  the  gastric 
juice,  be  acted  on  by  bile,  digestion  begins  anew  as 
soon  as  the  pancreatic  juice  is  added.  This  renewal  of 
digestion  does  not  take  place  unless  the  chyme  have 
first  been  subjected  to  the  interruption  of  digestion  by 
the  bile  ;  so  the  interruption  by  the  bile  seems  needful 
to  render  the  pancreatic  juice  active,  and  the  order 
of  succession  would  be  (i.)  gastric  juice  (ii.)  bile  (iii.) 
pancreatic  juice.  J  This  is  somewhat  in  opposition  to 
the  experience  of  physiologists  who  find  that  digestion 
goes  on  much  the  same  in  the  intestines  after  tying  the 
common  duct ;  and  especially  to  those  experiments  of 
Bidder  and  Schmidt  who  found  all  the  elements  of  the 
food  well  digested,  save  only  the  fats  and  oils.§ 

Tiedemann  and  Gmelin,||  Frerichs,^  and  an  observer 
so  late  as  Lucien  Corvisart,**  taught  that  it  was  not  the 

•  Claude  Bernard,  Legons  de  Physiologie  exp.  Paris,  1856,  t.  ij.  p,  421. 

f  John  C.  Dalton,  A  Treatise  on  Htiman  Physiology,  Philadelphia,  1871,  Fifth  ed. 
p.  180. 

■    X  Claude  Bernard,  op.  cit.  t.  ij.  p.  441.     See  the  observations  of  Heidenhain  on 
the  pancreatic  juice  and  bile  below,     (p.  143.) 

§  See  above,  p.  136. 
,    II  Tiedemann    and  Gmelin,   Recherches    experimentales,   etc.   sur   la   digestion, 
Jourdan's  transl.  Paris,  1827,  Partie  ii.  p.  395. 

IT  Frerichs,  Wagner's  Handw.  d.  Phys.   Braunschweig,   1846,  Bd.   iii.   Abth.  i. 
p.  834. 

**  Lucien  Corvisart,  Comptes  rendus,  1857,  ^-  ^^i^.  p.  720. 


142  Action  of  Bile  upon  the 

albuminous  parts  of  the  chyme  that  were  thrown  down 
by  contact  with  the  bile,  but  the  mucus  and  colouring 
matters  of  the  bile  itself.  Briicke  has  tried  to  disprove 
this  by  removing  the  mucus  of  the  bile  by  render- 
ing the  bile  acid  with  phosphoric  acid,  filtering,  and 
then  adding  the  filtrate  to  chyme ;  there  is  thrown 
down  an  abundant  white  precipitate,  composed  of  pep- 
tones.* Schiff  criticises  this,  for  he  says  that  although 
Briicke's  statements  are  true,  yet  his  interpretation  is 
false.  They  prove  nothing  about  the  physiological  action 
of  the  bile  upon  the  chyme.  Schiff  finds  that  it  is 
only  when  the  bile  is  rendered  more  acid  than  the 
gastric  juice,  that  a  precipitate  of  peptones  is  thrown 
down.  He  does  not,  however,  deny  that  bile  throws 
down  peptones.  Indeed,  he  recommends  this  humour 
as  a  substitute  for  Millon's  reagent  in  ascertaining  the 
presence  of  albuminates  not  thrown  down  by  heat.f 

According  to  Burkart  the  bile  has  a  very  distinct 
action  upon  the  gastric  juice.  A  precipitate  is  thrown 
down  which  on  examination  is  found  to  be  a  mixture  of 
the  pepsin  of  the  gastric  juice  with  the  bile  acid,  and 
the  supernatant  fluid  is  devoid  of  any  digestive  power.  J 
This  precipitation  Burkart  thinks  is  due  to  the  presence 
of  glycocholic  acid  in  the  bile,  not  to  taurocholic  acid.§ 
The  acid  of  the  gastric  juice  separates  the  glycocholic 
acid  from  its  base  and  this  acid  is  thrown  down  with 
the  pepsin  mechanically  adhering. 

Hammarsten  finds  that  the  digestive  power  of  the 
gastric  juice  is  destroyed  by  the  bile  of  many  species 
of  mammals,  and  also  of  birds  and  fishes.  He  thinks 
it  may  be  a  common  property  of  the  bile  of  all  verte- 
brate animals. 

*  Briicke,  Moleschott's  Untcvsiuhungen  zur  Nattirlchrc,  Giessen,  1862,  Bd.  viii. 
P-  335- 

f  M.  Schiff,  Arch.f.  d.  gcs.  Phys.  1870,  Bd.  iii.  p.  620. 
X  Burkart,  ibid.  1868,  Bd.  i.  p.  208. 
§  Idem,  ibid.  1S69,  Bd.  ii.  p.  182. 


Gastric  and  Pancreatic  Digestion.  143 

He  further  finds  that  a  precipitate  is  not  always 
formed  by  the  addition  of  bile  to  the  gastric  juice,*  but 
only  when  the  gastric  juice  contains  albumen  ;  and  that 
the  digestive  power  of  the  gastric  juice  may  be  taken 
away  even  while  the  fluid  remains  quite  clear.  The 
pepsin,  however,  is  not  decomposed  by  the  bile  acids, 
for  it  can  be  found  again.  Cubes  of  hard-boiled  white 
of  tgg  or  shreds  of  fibrin  are  not  acted  on  at  all  by 
gastric  juice,  if  they  be  kept  beforehand  for  a  few  hours 
in  a  mixture  of  gastric  juice  and  bile,  or  of  hydrochloric 
acid  and  bile.  This  is  due  to  some  union  between  the 
bile  and  the  albumen  ;  for  he  found  in  the  experiments 
just  mentioned  that  the  amount  of  solids  in  the  gastric 
juice  always  decreased,  while  the  weight  of  the  cubes 
of  hard-boiled  white  of  tgg  increased.  Apparently  there 
is  a  chemical  union  between  the  bile  acids  and  the 
albumen. 

He  finds  also  that  glycoeholic  acid  is  less  active  than 
bile  itself,  and  that  taurocholic  acid  is  more  active  than 
glycoeholic  acid  in  destroying  the  digestive  properties  of 
the  gastric  juice.  In  this  matter  he  is  in  direct  contra- 
diction with  Burkart.  He  thinks  it  possible  also  that 
the  other  elements  of  the  bile  may  have  some  share  in 
destroying  the  power  of  pepsin ;  but  as  no  means  are 
known  of  dissolving  cholestearin  or  the  pigments  but  by 
agents  which  would  at  the  same  time  greatly  disturb 
digestion,  the  question  at  present  cannot  be  settled. f 

In  contrast  to  the  action  of  bile  upon  gastric  juice, 
Heidenhain  found  that  when  bile  is  added  to  pancreatic 
juice  in  action,  the  process  is  not  put  a  stop  to,  but  is 
rather  favoured.  J 

According  to   Hoppe-Seyler's  observations,  the  pan- 

*  This  exactly  agrees  with  the  statement  of  Claude  Bernard,  who  found  that 
no  precipitate  followed  the  addition  of  bile  to  the  gastric  juice  from  an  animal 
fasting.     {Legons  de  Physiologic  exp.  Paris,  1856,  t.  ii.  p.  422.) 

t  O.  Hammarsten,  Arch.f.  d.  ges.  Phys.  1870,  Bd.  iii.  p.  53. 

X  Heidenhain,  ibid.  1875,  Bd.  x.  p.  579. 


144  -V  ^^^  Natural  Purge 

creatic  juice  does  not  seem  to  split  up  the  bile  acids 
into  cholalic  acid,  taurin,  and  glycocoll,  with  any  very 
great  rapidity.* 

I  have  not  met  with  any  direct  experiments  as  to 
the  action  of  the  bile  upon  the  succus  enteriais,  but 
the  bile  is  also  said  to  stimulate  the  secretion  of  the 
intestinal  juice,  and  to  increase  the  peristaltic  move- 
ments.f  In  favour  of  this,  Tiedemann  and  Gmelin 
found  that  the  faeces  of  animals  whose  bile  ducts  had 
been  tied  were  very  firm,  and  that  the  dogs  were  cos- 
tive.:|:  The  same  thing  has  been  noted  in  dogs  in 
whom  a  biliary  fistula  has  been  set  up.§ 

Eberle  found  that  the  bile  acted  on  the  bowels  as 
an  irritant,  increasing  their  movements,  and  causing 
an  abundant  secretion  from  the  mucous  membrane  ;|| 
and  Schiilein  has  lately  said  that  the  administration  of 
the  bile  acids,  whether  by  the  mouth  or  by  the  veins, 
is  followed  by  purging  and  vomiting ;  and  that  cholalic 
acid  is  more  active  in  this  way  than  glycocholic  or  tau- 
rochohc  acid.  He  thus  thinks  it  Hkely  that  the  bile 
may  increase  the  peristaltic  movements  of  the  intes- 
tines,^ as  Eberle  has  suggested. 

Another  use  of  the  bile  was  formerly  thought  to  be 
the  neutralisation  of  the  acid  of  the  gastric  juice  ;**  but 

*  Hoppe-Seyler,  Arch.f.  path.  Anat.  1863,  Bd.  xxvi.  p.  532. 

f  Saunders  thought  this  to  be  its  principal  office.  {A  Treatise  on  the  Structure, 
Economy,  and  Diseases  of  the  Liver,  Lond.  1803,  Third  ed.  p.  151.)  and  Sir  Thomas 
Browne  [Pscitdodoxia  Epideniica  or  Enquiries  into  Vulgar  and  Common  Errors,  Book 
iii.  Chapter  ii.  London,  1650,  Sec.  Ed.  page  88.)  expresses  the  common  belief  of  the 
17th  and  i8th  centuries  when  he  says  :  Choler  is  the  naturall  glister,  or  one  excre- 
tion whereby  nature  excludeth  another ;  which  descending  daily  into  the  bowels, 
extimulates  those  parts,  and  excites  them  unto  expulsion.  And  therefore  when  this 
humour  aboundeth  or  corrupteth,  there  succeeds  oft  times  a  cholcrica  passio  ;  that 
is,  a  sudden  and  vehement  purgation  upward  and  downward. 

I  Tiedemann  and  Gmelin,  op.  cit.  Partie  ii,  pp.  47  and  70. 
§  Schwann,  Bidder  and  Schmidt,  //.  ciit. 

II  Eberle,  Physiologic  der  Vcrdauung,  Wiirzburg,  1834,  p.  314. 
IT  M.  Schiilein,  Zcitschriftf.  Biologic,  1877,  ^^-  '^'''-  P*  ^J^- 

••  Boerhaave  is  said  by  Tiedemann  and  Gmelin  to  have  been  a  supporter  of  this 
theory.      (Tiedemann  and  Gmelin,  op.  cit.  Partie  i.   p.  384.)     I   can  hardly  think 


Antacid  or  Antiseptic.  145 

as  the  bile  is  commonly  neutral  in  reaction,  and  but 
rarely  alkaline,  it  is  clear  that  this  cannot  be  its  chief 
office.  This  view  prevailed  longer  than  natural ;  for  it 
was  adopted  by  C.  H.  Schultz  in  his  theories  on  the 
amount  of  the  bile,  and  these  again  were  brought  into 
prominence  by  Liebig.* 

The  bile  is  thought  to  hinder  putrefaction.  Bidder 
and  Schmidt, t  with  other  observers,  noted  the  disgust- 
ing smell  of  the  fasces  and  flatus  of  dogs  in  whom  the 
bile  had  been  diverted  from  the  intestines.  The  same 
thing  is  said  to  be  seen  in  jaundice,  though  I  can  hardly 
assent  myself  to  this  as  a  general  rule.  The  bad  smell 
is  attributed  to  the  lack  of  the  antiseptic  action  of  the 
bile.  Saunders  attributed  the  antiseptic  powers  of  bile 
to  its  bitterness,  and  found  by  experiment  that  bile 
became  putrid  less  readily  than  blood. J  Von  Gorup 
Besanez  thinks  the  antiseptic  powers  of  the  bile  due 
to  the  bile  acids.  He  put  meat  and  albumen  into  a 
solution  of  the  bile  acids,  and  kept  the  mixture  for  48 
hours  at  the  temperature  of  the  body.  At  the  end  of 
this  time  there  was  no  trace  of  putrefaction  ;  while 
meat  and  albumen  put  into  plain  water  and  treated  in 
the  same  way  gave  distinct  signs  of  putrefaction  at  the 


that  Boerhaave  was  of  opinion  that  the  bile  had  an  alkaline  reaction.  Speaking 
of  the  properties  of  the  cystic  bile,  he  says:  "nee  alcalica  est,  nee  acida."  {Opera 
Omnia  Mcdica,  Venetiis,  1757,  p.  20.  Institutiones  Medicse,  §  gg.)  On  the  other 
hand  he  says  a  little  later  on  :  (p.  22  §  107)  "  Bills  Alcalina  acidum  Chylum  fixum 
in  salsum  volatile  Alcalescens  immutans  ;  Pancreatic^  Lymphje  acor  et  cum  bile 
Alcalina  fervor ;  .  .  .  .  et  innumerae  tales  hypotheses,  damnos«,  dum,  regulas 
dant  faciundse  Medicinae." 

Kemp  {Lond.  Med.  Gaz.  1845,  vol.  i.  p.  77.)  says  he  has  examined  200  samples 
of  bile  and  found  them  all  neutral. 

*  See  p.  g4  of  this  work. 

•f  Bidder  and  Schmidt,  op.  cii,  p.  104. 

H.  Hoffmann  is  said  to  have  an  important  paper  on  the  antiseptic  powers  of  the 
bile,  (Haser's  Archiv  1844,  Bd.  vi.  p.  157.)  but  I  have  not  been  able  to  see  a  copy 
of  this  in  London. 

X  Saunders,  op.  cit.  pp.  136  and  155. 


146  Antiseptic  Powers  of  Bile. 

end  of  24  hours.*  He  found  also  that -fermentation  set 
in  much  later  when  bile  was  mixed  with  syrup,  urine, 
and  the  like,  than  without.  This  experiment  has  been 
confirmed  by  Claude  Bernard,  who  found  that  bile  at 
once  checked  the  fermentation  of  yeast  from  the  sto- 
mach of  a  dog-t 

More  lately  Stolnikoff  has  made  a  few  experiments  in 
Hoppe-Seyler's  laboratory  at  Strassburg  on  this  point. 
Bile  and  water  ;  fibrin,  bile,  and  water  ;  fibrin,  fat,  and 
water ;  and  fibrin,  fat,  bile,  and  water  were  left  in 
bottles  from  the  middle  of  June  to  the  middle  of  August, 
and  the  gases  given  out  collected  over  mercury.  The 
bile  simply  mixed  with  water  had  given  out  no  gas  ; 
but  the  mixture  of  fibrin  and  fat  without  bile  had  given 
out  most  of  all.  The  gas  showed  92  per  cent,  of  car- 
bonic acid.  The  contents  of  the  bottles  showed  the 
bile  acids  split  up  into  cholalic  acid,  taurin,  and  glycocoll, 
as  might  have  been  looked  for.  Stolnikoff  concludes 
that  bile  is  able  for  a  short  time  to  delay  putrefaction, 
but  not  to  hinder  it  altogether,  as  the  bile  and  water  itself 
had  split  up  into  new  products,  although  no  gas  had 
been  given  off.  Stolnikoff  does  not  think  that  the 
office  of  the  bile  is  to  stop  putrefaction  in  the  intestines, 
but  rather  to  favour  absorption.  J 

Haller  thought  that  the  use  of  the  bile  was  to  aid  in 
the  solution  of  the  food,  and  to  form  one  homogene- 
ous mass  with  mucus,  oil,  and  water,  by  trituration  and 
the  peristaltic  action  of  the  bowels. § 

Changes  of  the  bile  in  the  intestines. — After  the  bile 
has  been   poured   into  the  duodenum,  and  done  what- 

♦  E.  von  Gorup-Besanez,  Unfcrsucliungcn  ucbcy  Gallc,  Erlangen,  1846,  pp.  48 
and  50.  The  first  of  these  experiments  was  made  with  the  same  result  by  Plainer. 
(Ueber  die  Natur  mid  den  Ntitzen  der  Galle,  Heidelberg,  1845,  P-  128.) 

f  Claude  Bernard,  reported  by  Donaldson,  American  journal  of  the  Medical 
Sciences,  1851.  Vol.  xxii.  p.  351. 

J  J.  Stolnikoff,  Zeitschriftf.phys.  Clicinic,  1878,  Bd.  i.  p.  343. 

§  Haller,  Elciii.  Phys.  Lugd.  Bat.  1764,  t.  vi.  p.  608. 


Changes  of  Bile  in  Intestine.  147 

ever  it  is  appointed  to  do,  whether  it  be  a  positive  harm 
to  the  process  of  digestion,  a  suggestion  which  in  the 
present  state  of  knowledge  may  perhaps  be  entertained  ; 
or  be  simply  an  indifferent  fluid ;  or  in  some  way  aid 
the  pancreatic  juice  ;  what  becomes  of  the  humour  ? 
Does  it  pass  entirely  out  of  the  body  with  the  faeces,  or 
is  it  absorbed  again  into  the  circulation  ? 

Liebig  and  his  followers  assumed  that  the  greater 
part  of  the  bile  was  absorbed  to  aid  in  the  combustion  of 
respiration.*  Mulder,  on  the  other  hand,  taught  that 
the  greater  part  of  the  bile  was  passed  out  by  the  anus,t 
while  Frerichs  held  that  neither  of  these  views  was 
wholly  correct,  J  at  the  same  time  stating  that  of  the 
bile  only  a  small  part  was  absorbed. 

Bidder  and  Schmidt,  in  order  to  settle  this  question, 
estimated  the  amount  of  bile  in  the  faeces  passed  in  five 
days  by  a  dog  weighing  8  kilogrammes.  The  faeces 
weighed  97*3  grm.  of  which  40*9  grammes  were  solid. 
Now  the  solids  of  the  bile  passed  in  five  days  would  be 
39*52  grm.  that  is  nearly  equal  to  the  solids  of  the 
faeces  ;  yet  the  faeces  showed  but  small  traces  of  the 
presence  of  bile.  Still  more  important  was  the 
amount  of  sulphur  in  the  faeces.  The  bile  of  dogs 
holds  about  6  per  cent,  of  sulphur :  so  that  in  39*52 
grm.  of  solid  bile,  there  should  be  nearly  2*37  grm.  of 
sulphur.  As  a  fact,  the  faeces  only  held  0*334  g^^^-  of 
sulphur ;  and  without  doubt  more  than  half  of  this 
came  from  the  numerous  hairs  in  which  the  faeces 
abounded. § 

It  was  said  by  Frerichs  in  1846  that  as  soon  as  the 


*  Liebig,  Animal  Chemistry,  London,  1842,  Gregory's  translation.  Sec.  Ed.  pp. 
60-66. 

f  Mulder,  U titer siichungen  iiber  die  Galle,  Frankf.  a.  M.  1847,  P-  ^o?'  He 
teaches  that  the  bile  begins  to  decompose  as  soon  as  it  is  secreted. 

%  Frerichs,  in  Wagner's  Handworterbicch  d.  Physiologie,  Braunschweig,  1846, 
Bd.  iii.  Abth.  i.  p.  839. 

§  Bidder  and  Schmidt,  op.  cit.  p.  217. 

L  2      . 


148  Decomposition  and  Absorption 

bile  entered  the  intestine,  the  bile  acids  broke  up  into 
taurin,  chloidic  acid,  and  dyslysin,  and  that  in  the  end 
only  dyslysin  could  be  detected.  The  pigment  is  de- 
scribed as  passing  from  green  into  brown,  and  at  last 
attaining  the  characters  of  the  colouring  matter  of 
some  gall  stones.*  The  cholestearin  at  this  time 
seems  to  have  been  neglected. 

But  in  1862  Hoppe  discovered  the  presence  of  free 
cholalic  acid  in  the  faeces  of  dogs,f  and  in  a  few  months 
the  same  observer  announced  that,  as  well  as  cholalic 
acid  in  quantity,  he  found  undecomposed  glycocholic 
and  taurocholic  acid  in  the  faeces  of  dogs  and  cows, 
and  certain  elements  of  the  bile  in  the  faeces  of  pigeons, 
and  in  guano  from  Peru.  He  estimated  the  amount 
of  cholalic  acid  in  the  fasces  of  a  dog  weighing  8  kilo- 
grammes and  fed  on  beef.  The  weight  of  the  faeces  for 
three  days  was  287  grammes,  and  the  amount  of  chola- 
lic acid  was  i*i  grm.  estimated  by  the  polariscope.  This 
equals  "36  grm  of  cholalic  acid  a  day,  or  '45  grm.  of 
taurocholic  acid.  Now  taking  Bidder  and  Schmidt's 
estimate  for  the  amount  of  solids  in  the  bile  excreted  by 
a  dog  of  this  weight  as  8  grm.  in  24  hours,  J  and  one  half 
of  this  as  made  up  of  bile  acids,  there  will  be  at  the 
most  only  half  a  gramme  out  of  4  grammes  of  bile  acids 
accounted  for  in  the  faeces.  What  becomes  then  of  the 
remaining  three  and  a  half  grammes  ? 

Hoppe-Seyler  analysed  the  contents  of  different  parts 
of  the  intestines  of  dogs  and  rabbits,  and  found  that 
though  the  splitting  up  of  the  taurocholic  acid  began  in 
the  small  intestine,  yet  it  chiefly  progressed  in  the 
large  intestine.  He  thinks  it  a  spontaneous  change  ; 
for  none  of  the  secretions  poured  into  the  intestine  con- 


*  Frerichs,  in  Wagner's  Haiidwui'tcfbiich   d.  Pliysiologic,  Braunschweig,  1846. 
Bd.  iii.  Abth.  i.  pp.  840  and  841. 

+  Hoppe,  Arcliiv.f.  path.  Anat.  1862,  Bd.  xxv.  p.  181. 
X  Sec  p.  100  of  this  work. 


of  Bile  in  Intestine,  149 

tains  a  ferment  capable  of  setting  the  change  in  motion : 
also  that  the  change  is  quite  analogous  to  that  of  the 
splitting  up  of  hippuric  acid,  and  notes  that  the  faeces 
of  dogs  hold  a  quantity  of  free  butyric  acid,  valerianic 
acid,  caproic  and  caprylic  acid,  products  of  decom- 
position in  the  large  intestine.* 

It  will  have  been  seen  above  that  Hoppe-Seyler  and 
his  followers  assert  that  the  bile  acids  become  decom- 
posed in  the  intestines  into  taurin  and  glycocoll,  with 
the  formation  of  free  cholalic  acid.  Uncombined  taurin 
and  glycocoll  are  not  found  in  the  faeces,  so  it  is 
probable  that  they,  or  the  products  of' their  decompo- 
sition, are  absorbed  again  into  the  blood.  Schultzen 
and  Nencki,  in  their  admirable  research  into  the  de- 
compositions which  lead  to  urea,  found  that  when  an 
animal,  the  amount  of  urea  in  whose  urine  was  constant, 
was  fed  with  glycocoll,  the  urea  was  at  once  increased 
to  an  amount  equivalent  to  the  amount  of  glycocoll 
ingested.  Glycocoll,  therefore,  on  its  way  through  the 
ceconomy  becomes  changed  into  urea,  and  in  this  way 
leaves  the  body.f  Taurin  would  also  seem  to  pass 
out  of  the  body  by  the  urine,  as  Salkowski  found  that 
in  man  taurin  given  by  the  mouth  again  appeared  in 
the  urine,  partly  as  unchanged  taurin,  but  in  great  part 
as  an  acid  containing  sulphur  and  nitrogen  (tauro- 
carbamic  acid)  the  normal  sulphates  not  being  in- 
creased.^ 

If  some  of  Ernst  Bischoff's  estimations  were  accepted 
as  representing  a  general  rule,  there  might  be  no  need 
of  discussing  further  the  fate  of  the  bile  in  the  intestines. 
He  found  the  faeces  rich  in  bile,  about  10  per  cent,  of 
unaltered  bile   acids,  while  the   cholalic  and  choloidic 

*  Hoppe-Seyler,  ibid.  1863,  Bd.  xxvi.  p.  519. 

f  Schultzen  and  Nencki,  Zeitschriftf.  Biologic,  1872,  Bd.  viii.  p.  132. 

\  Salkowski,  Berichte  der  deiitschcn  chem,  Gesellschaft  zii  Berlin,  1872,  Jahrg. 
V.  p.  637.  See  also  an  abstract  by  himself  in  Virchow  and  Hirsch's  Jahreshcricht 
f.  1873,  Bd.  i.  p.  159.. 


150  Supposed  Circulation  of  the  Bile 

acids  were  not  more  than  i  per  cent.  Altogether  he 
thinks  that  man  passes  daily  per  anum  about  5  grammes 
of  solid  bile.*  Now  5  grammes  of  solid  bile  would  be 
about  the  amount  secreted  daily  by  the  liver  in  the  cases 
of  biliary  fistula  in  man  observed  by  Dr.  Robinson  and 
Krumptmann,t  and  Leyden  adopts  2  to  4  grammes  as 
the  amount  of  bile  acids  daily  secreted  by  the  liver. J 
Calculations  of  this  sort  must  not  be  pressed  too  far, 
as  there  appear  to  be  as  great  variations  in  the  amount 
of  bile  secreted  by  man  as  by  any  other  animal. 

In  i86g,  Schiff  announced  that  the  bile  acids  and 
bile  pigments  are  again  absorbed  into  the  portal 
circulation  and  again  excreted  by  the  liver.  In  a 
dog,  upon  whom  a  biliary  fistula  had  been  made, 
the  amount  of  bile  excreted  was  about  2  C.C.  in 
20  minutes.  If  180  C.C.  of  fresh  ox  bile  were  now 
injected  into  the  duodenum,  a  surprising  increase 
of  the  amount  of  bile  took  place  ;  so  that  in  a  very 
short  time  10  C.C.  of  bile  could  be  collected  in  20  min- 
utes from  the  fistula,  and  at  the  end  of  an  hour  8*5 
C.C.  in  20  minutes.  Schiff  then  availed  himself  of  a 
statement  of  Heidenhain's,  that  the  bile  of  the  guinea- 
pig  gives  no  reaction  with  Pettenkofer's  test.  He  esta- 
blished a  fistula  on  a  guinea-pig,  and  found  no  decided 
reaction  in  the  bile  when  tested  by  Pettenkofer's  test ; 
ox  bile  was  then  injected  into  the  duodenum,  and  in  half 
an  hour,  and  up  to  i,  2,  or  3  hours  after,  the  bile  gave  a 
marked  reaction  with  Pettenkofer's  test,  just  as  if  ox  bile 
had  been  diluted  with  2  or  3  times  its  volume  of  water. 
As  to  the  pigments,  the  natural  colour  of  the  bile  of 
dogs  is  a  golden  yellow  ;  when  ox  bile  was  introduced 
into  the  duodenum  of  dogs,  the  bile  became  dark  and 
brown. 

*  Ernst  BischofT,  Zciischrift  f.  rat.  Med.  1864,  Bd.  xxi.  p.  143. 

f  See  p.  97  of  this  work. 

X  Leyden,  Dcitrdge  zur  Pathologic  Acs  Icterus,  Berlin,  1866,  p.  55. 


between  the  Liver  and  Intestine.  151 

The  phaenomena  prove  in  Schiff's  opinion  that  there 
is  a  circulation  of  the  bile,  as  well  as  of  the  blood  ;  that 
the  bile  is  poured  out  by  the  liver  into  the  intestine, 
there  again  to  be  taken  up  by  the  mesenteric  vessels, 
carried  to  the  liver,  and  again  excreted  into  the  duo- 
denum.* In  another  article,  he  repeats  his  belief  that 
the  secretion  of  bile  is  almost  wholly  dependent  on  ab- 
sorption from  the  intestine,  and  that  if  the  bile  be  cut 
off  from  the  intestine,  little  or  no  bile  is  secreted. f 

Theodor  Laffter,  under  Heidenhain's  direction,  has 
repeated  Schiff's  experiments,  and  differs  from  him  con- 
siderably in  his  results.  When  ox  bile  was  injected 
into  the  duodenum  of  guinea  pigs,  a  very  slight  increase 
of  the  amount  of  bile  was  seen  in  some,  in  others  a  de- 
crease. Laffter  does  not  attribute  this  decrease  to  the 
action  of  the  bile,  but  to  a  peculiarity  of  the  animal. 
Laffter  agrees  with  Schiff  in  announcing  an  increase  in 
the  solid  bile,  but  the  amount  seems  to  me  so  small  that 
it  may  easily  be  within  the  boundaries  of  physiological 
variation.  In  one  matter  Laffter  has  made  a  curious 
observation  ;  he  finds  that  colouring  matters,  such  as 
rhubarb  and  indigo-sulphate  of  soda,  injected  into  the 
duodenum,  very  rapidly  appear  in  the  bile ;  in  one  read- 
ing of  the  text,  Laffter  may  be  thought  to  say  within  a 
minute  after  the  injection  into  the  duodenum. J 

Following  upon  Laffter,  Prince  Tarchanoff  entered 
upon  a  research  to  show  that  the  liver  has  also  the  power 
of  rapidly  excreting  other  colouring  matters.  If  blood 
colouring  matter  or  bilirubin  be  injected  into  the  veins 
of  a  dog  with  a  biliary  fistula,  a  great  increase  of  the 
water  and  pigments  of  the  bile  follows. § 

*  M.  Schiff,  Giorn.  di  Scienze  Natiirali  ed  Econ.  Palermo,  i86g,  vol.  iv.  p.  g, 

f  M.  Schiff,  Arch.f.  d.  ges.  Phys.  1870,  Bd.  iii.  p.  598. 

J  Theodor  Laffter,  Versuche  ziir  Physiologie  der  Gallensccrction,  Diss.  Inaug. 
Breslau,  1873.  It  is  not  so  clearly  expressed  as  I  could  wish  that  this  last  colour- 
ing matter  was  injected  into  the  duodenum.  I  am  indebted  to  Dr.  Lauder  Brunton 
for  the  opportunity  of  seeing  the  original  dissertation. 

§  Johannes,  Fiirst  Tarchanoff,  Arch.f.  d.  ges.  Phys.  1874,  Bd.  ix.  p.  329. 


152  Supposed  Circulation  of  Bile 

Huppert's  observations  are  generally  quoted  as  if 
they  gave  aid  to  Schiff's  belief  that  the  bile  acids  are 
excreted  by  the  liver.  He  injected  a  certain  quantity 
of  bile  acids  into  the  circulation  of  a  rabbit  in  whom 
a  biliary  fistula  had  been  set  up,  and  found  that  the 
liver  excreted  about  the  fourth  to  the  third  part  of  the 
bile  acids  injected.* 

Socoloff  has  repeated,  in  Hoppe-Seyler's  laboratory, 
some  experiments  like  those  of  Schiff,  but  he  has  not 
obtained  precisely  the  same  results.  After  the  in- 
jection of  the  glycocholate  of  soda  into  the  veins  or 
stomach  of  dogs,  he  found  indeed  that  there  w^as  an 
increase,  very  marked,  of  the  amount  of  bile  secreted. 
And  this  increase  took  place,  as  Schiff  found  it,  v^ithin 
15  minutes  after  the  injection.  With  this  increase  of 
the  bile  itself,  there  was  always  a  marked  decrease  of 
the  amount  of  bile  acid  salts.  There  was  not  the  least 
increase  of  the  solids  of  the  bile.  Now  if  this  be  main- 
tained, a  blow  will  certainly  be  dealt  to  the  views  of 
Schiff  and  his  followers,  as  Schiff  himself  expressly 
states  that  there  is  an  increase  in  the  amount  of  the 
solids  of  the  bile.f 

Socoloff  notes  also  that  in  Huppert's  experiments 
the  increase  of  bile  after  the  injection  of  bile  acids 
was  first  noted  in  the  second  hour,  just  as  Bidder  and 
Schmidt  did  in  their  experiments  without  injection. 
He  criticises  justly  also  Schiff's  observations  on  guinea 
pigs,  noting  that  Pettenkofer's  test  is  not  enough 
alone  to  enable  a  man  to  assert  the  presence  of  bile 
acids,  but  that  the  bile  acids  should  be  crystallised  out, 
as  Socoloff  has  done.  J 

It  may  be  noted  also  that   Laffter§  and   KiilzH   deny 

*  Huppert,  Arcliiv  dcr  Ilcilkundc,  1864,  p.  244. 

f  Schiff,  Arch.f.  d.  ges.  Phys.  1870,  Bd.  iii.  p.  599. 

\   Socoloff,  ibid.  1875,  Bd.  xi.  p.  166. 

§  Laffter,  op.  cit.  p.  11.     Work  done  in  Heidenhain's  laboratory. 

II  Kiilz,  Virchow  and  Hirsch's  Jahresbericht  f.  1875,  Bd.  i.  p,  219. 


and  Absorption  in  Intestine.  153 

the  statement  of  Schiff  that  the  bile  of  guinea  pigs 
gives  no  reaction  with  Pettenkofer's  test.  And  it  must 
be  owned  that  it  does  seem  highly  improbable  that  the 
bile  of  a  vertebrate  should  be  without  evidence  of  the 
presence  of  bile  acids. 

Tappeiner  has  also  made  estimations  on  the  absorp- 
tion of  bile  acids  by  the  small  intestine.  Dogs  were 
fasted  for  24  hours,  and  then  a  certain  quantity  of  dog's 
bile,  or  a  solution  of  glycocholate  of  soda,  injected  into 
a  tied-off  part  of  the  small  intestine.  After  the  bile 
acid  salt  or  the  gall  had  been  left  in  the  bowel  from  3 
to  5  hours,  the  amount  of  bile  acids  and  of  sulphur  was 
estimated.  In  the  upper  part  of  the  small  intestine, 
the  duodenum  and  jejunum,  the  whole  of  the  sulphur  of 
the  bile  was  found  again  ;  in  the  ileum,  never  more 
than  one  third.  Of  glycocholate  of  soda  none  was  ab- 
sorbed in  the  duodenum  ;  but  in  the  jejunum  and  ileum, 
never  more  than  one  half  could  again  be  found. 

Tappeiner  refuses  to  admit  a  chemical  change  as  the 
cause  of  a  decrease  in  the  amount  of  bile  acids  found. 
The  first  step  in  a  chemical  change  would  be  the 
decomposition  of  the  bile  acids  into  cholalic  acid,  tau- 
rin,  and  glycocoll.  Now  it  was  found  that  taurin  is 
readily  absorbed  by  the  intestines  of  dogs  ;  but  when 
taurocholic  acid  was  injected  into  the  jejunum,  the 
whole  quantity  injected  was  found  again.*  It  may  be 
admitted  that  there  is  no  decomposition  in  the  parts  of 
the  intestines  where  the  amount  of  bile  acids  injected 
was  again  recovered,  but  this  will  hardly  be  allowed  to 
hold  good  for  the  ileum,  where  only  one  half  or  one 
third  of  the  bile  acids  could  again  be  recovered,  and 
which  may  therefore  have  undergone  the  decomposition 
in  question  before  they  were  absorbed. 

Amongst  the  older  authors,  Tiedemann  and  Gmelin 

*  Tappeiner,  in  von  Buhl's  Mitt,  aus  d.  path.  Inst,  zu  Munchen,  Stuttgart,  187S, 
p.  218. 


154  Cholestearin  as  Product  of  Liver. 

found  cholestearin  in  the  contents  of  the  small  intestine  of 
certain  mammals,  and  in  the  large  intestine  of  the  calf.* 
But  Dr.  Austin  Flint,  the  younger,  is  of  opinion  that  no 
cholestearin  can  be  found  in  normal  faeces,  only  a 
product  of  the  decomposition  of  cholestearin,  named 
serolin  by  Boudet,  but  which  Dr.  Flint  calls  stercorin-f 
The  elimination  of  cholestearin  he  looks  upon  as  a  most 
important  office  of  the  liver.  Hoppe-Seyler,  commen- 
ting upon  the  observations  of  Dr.  Austin  Flint,  says 
that  he  has  always  found  cholestearin  in  the  faeces  of 
dogs,  oxen  and  men  ;  and  he  does  not  doubt  that  Dr. 
Flint's  stercorin  and  Boudet's  serolin  are  but  impure 
cholestearin. J  Dr,  Flint's  theory  would  in  this  case 
fall  to  the  ground,  if  Hoppe-Seyler's  facts  be  accepted  ; 
and  I  think  that  evidence  offered  by  this  distinguished 
chemist  on  a  matter  like  the  finding  of  cholestearin  will 
be  hard  to  be  overturned. 

Beneke  also  looks  upon  the  excretion  of  cholestearin 
by  the  liver  as  a  function  most  important  to  the 
ceconomy ;  but  he  does  not,  like  Dr.  Flint,  think 
cholestearin  a  mere  excremental  product.  Rather  not- 
ing the  wide-spread  distribution  of  this  body  in  both 
the  animal  and  vegetable  kingdom,  being  found  in  the 
seed  of  both  plants  and  beasts,  in  the  milk,  in  the 
chyle,  the  serum  and  corpuscles  of  the  blood,  in  the 
marrow  of  bones,  and  above  all  in  the  nervous  system, 
he  thinks  it  must  serve  other  uses  than  that  of  a  mere 
excrement.  The  liver  is,  according  to  Beneke,  the 
organ  in  which  cholestearin,  and  its  attendant,  leci- 
thin, are  formed ;  with  the  bile  they  pass  into  the 
intestine,  and  thence  all  over  the  body.  In  Beneke's 
view,  therefore,  cholestearin  and  lecithin  would  be  two 

•  Tiedemann  and  Gmelin,  op.  cit.  partie  i.  pp.  395  and  404. 

f  Austin  Flint,  Rechcrchcs  cxp.  sur  une  nouvclle  fonction  dxi  foie,  Paris,  1868. 
passim. 

X  Hoppe-Seyler,  in  Virchow  and  H'n^.zW?,  Jahreshcricht  f.  1868,  Bd.  i.  p.  97. 
See  also  Arch.  f.  path.  Anat.  1863,  Bd,  xxvi.  pp.  527,  et  scq. 


End  of  the  Bile.  155 

of  the  most  important  physiological  compounds  and 
certainly  the  most  important  of  those  found  in  the  bile.* 

To  what  purpose,  then,  serves  the  bile  ?  It  cannot 
be  looked  upon  solely  as  an  excrement,  for  it  has  been 
seen  what  deep  changes  in  nutrition  follow  its  diversion 
from  the  body.  There  is  no  evidence  that  it  is  neces- 
sary for  the  completion  of  the  process  of  digestion  in 
the  stomach  or  intestines ;  indeed  it  may  be  said  by 
some  physiologists  that  it  does  harm  to  the  process  in 
either  viscus.  The  view  that  it  acts' as  a  sort  of  natural 
purge  has  little  against  it ;  but,  at  the  same  time,  there 
is  but  little  in  its  favour.  As  to  the  power  of  the  bile 
in  arresting  putrefaction,  it  would  seem  that  it  must 
be  small,  if,  as  soon  as  it  arrives  in  the  intestine,  it 
begin  itself  to  undergo  putrefactive  changes.  The  view 
that  the  bile  neutralises  the  acid  of  the  chyme  must  fall 
with  the  establishment  of  the  fact  that  the  bile  is  not 
alkaline  but  neutral  in  reaction.  The  only  office 
which  remains  to  it  is  that  of  emulsifying  fats,  a  pro- 
perty known  to  the  Greeks  2200  years  ago,  and  of 
changing  starch  into  sugar.  It  is  melancholy  to  find 
that  in  so  many  years  nothing  more  is  known  with 
certainty  as  to  the  uses  of  this  long-studied  humour. 

It  has  seemed  to  me  that  physiologists  are  drifting  into 
the  belief  that  the  office  of  the  bile  is  not  to  act  upon  the 
chyme  or  to  assist  in  the  first  digestion  of  aliments. 
Rather  its  office  is  to  pass  into  the  intestine,  there  to 
undergo  changes  itself,  the  products  of  decomposition 
being  absorbed  into  the  blood,  and  leaving  the  body  by 
the  urine.  If  it  be  admitted  that  the  bile  acids  be  de- 
composed before  they  be  absorbed,  it  is  most  probable 
that  they  split  up  into  glycocoll,  taurin,  and  cholalic 
acid.  The  glycocoll,  it  has  been  seen  above,  is  one  of 
the  bodies  which,  when  taken  into  the  intestine,  appears 

*  Beneke,  Grimdlinien  der  Pathologie  des  Stoffwechsels,  Berlin,  1874,  p.  194.  • 


156  End  of  the  Bile. 

in  the  urine  as  urea ;  taurin,  in  like  manner,  appears  in 
the  urine,  probably  furnishing  the  unoxydised  sulphur  of 
this  secretion,  though,  according  to  Salkowski*  it  can 
no  lone:er  be  thouo:ht  that  in  man  it  is  the  source  of  the 
oxydised  bodies,  the  sulphates.  In  rabbits,  the  inges- 
tion of  taurin  is  still  followed  by  a  great  excess  of  sul- 
phates in  the  urine.  The  cholalic  acid  would  appear  to 
leave  the  body  by  the  faeces  ;  but  a  theory  might  be 
made  by  adopting  Schiff's  view  of  a  circulation  of  the 
bile  ;  supposing  a  salt  of  cholalic  acid  to  be  absorbed 
and  conveyed  to  the  liver,  and  there  to  unite  with  freshly 
made  taurin  and  glycocoll,  and  again  to  be  excreted  by 
the  bile.  Of  the  destiny  of  the  bile  pigments,  little  has 
been  yet  said  ;  by  some  it  is  thought  that  they  undergo 
oxydation*!*  in  the  intestines ;  by  others,  reduction  ;J 
but  the  product  of  the  change,  whatever  it  may  be,  is 
called,  by  Vanlair  and  Masius,  stercobilin  ;§  a  pigment 
which  is  closely  allied  to  that  colouring  matter  of  the 
urinenamedurobilinbyJaffe.il  It  thus  becomes  pos- 
sible that  the  bile  pigments,  after  suffering  whatever 
chemical  change  they  may  be  destined  to  undergo  in 
the  bowel,  are  absorbed  into  the  blood  and  excreted  by 
the  urine  as  colouring  matter,  while  the  remainder 
passes  out  with  the  faeces.  The  end  of  the  bile  would 
thus  seem  to  be  excretion  by  the  urine  ;  a  view  not 
altogether  new,  for  it  was  taught  by  physiologists  six- 
teen hundred  years  ago  that  the  urine  was  formed,  in 
the  liver,  and  separated  by  the  kidneys  ;  and  those  who 
come  after  us  may  judge  whether  the  nineteenth  century 
have  made  any  real  progress  in  this  matter  compared 
with  the  age  of  Galen. 

*  Salkowski,  Virchow  and  Hirsch's  yahresberichtf.  1873,  Bd.  i.  p.  159. 
f  Heynsius  and  Campbell,  Arch.  f.  d.  gcs.  Phys.  1871,  Bd.  iv.  p.  497. 
J  Maly,  Annalcn  d.  Chcmie  11.  Pharm.  1872,  Bd.  clxiii,  p.  77. 
§  Vanlair  and  Masius,  Ccnlralblatt  f.  d.  mcd.  Wiss.  1871,  p.  369. 
II  Jaffe,  Arch.f.  path.  Anat.  1869,  Bd.  xlvii.  p.  423, 


CHAPTER   VIII. 

Action  of  Drugs  upon  the  Secretion  of  the  Bile. 

The  notion  of  a  drug  which  should  have  a  special 
action  on  the  bile  is  as  old  as  Hippocrates,*  although 
the  word  cholagogue  does  not  appear  to  have  been  much 
used  before  the  time  of  Galen.  Certain  drugs  were 
commonly  supposed  in  former  times  to  increase  the 
amount  of  the  bile  secreted  by  the  liver,  because  the 
patient  passed  stools  of  yellow  or  dark  colour  after  the 
the  drug  had  been  administered.  It  is  clear  that  no  rea- 
soning can  be  more  fallacious.  The  colour  of  the  stools 
depends  not  so  much  on  the  amount  of  bile  secreted, 
as  on  the  length  of  time  that  the  faeces  have  sojourned  in 
the  intestines,  or  on  the  diet  of  the  patient.  If  they  should 
be  hurried  through  the  intestines,  they  may  even  con- 
tain unaltered  bile  ;  if  the  patient  have  taken  abun- 
dance, of  milk,  they  will  be  almost  colourless.  It  is 
plain  that  no  trustworthy  information  can  be  had, 
save  from  the  observation  of  the  amount  of  bile  dis- 
charged by  a  biliary  fistula.  In  man,  it  has  already 
been  said,  biliary  iistulse  are  rare,  and  in  this  way 
knowledge  has  been  but  little  increased. 

In  Westphalen's  case,  indeed,  a  dose  of  calomel  (1*3 
gramme  =  20  grains)  was  once  given  to  the  patient, 
but  without  causing  any  increase,  rather  a  decrease,  of 
the  amount  of  bile.*]'  Quinine,  given  in  doses  of  2 
grammes,  (30  grains)  could  not  be  found  in  the  bile. 

Observations  on  animals  with  artificial  biliary  fistula 
are,  then,  the  only  means  by  which  information  is  to  be 
had  ;    and  Hermann  Nasse,  the  first  to  make   observa- 

*  Hippocrates,  De  nat.  horn.  Cap.  5,  Littre's  ed.  t.  vi.  p.  42. 

f  Westphalen,  DeiUsches  Arch.  f.  klin.  Med.  1873,  Bd.  xi.  pp.  598  and  600. 


158  Mercury  as  Cholagogue. 

tions  on  the  amount  of  bile  secreted  by  the  dog,  was 
also  the  first  to  test  the  effect  of  drugs  on  the  bile.  He 
reports  that  calomel  increased  the  amount  of  fluid  bile 
but  decreased  the  solids,  and  that  large  doses  of  car- 
bonate of  soda  decreased  both  the  fluid  and  solid  bile.* 
As  the  preparations  of  mercury  are  those  which  have 
enjoyed  the  greatest  reputation  for  increasing  the  secre- 
tion of  bile,  it  will  be  found  convenient  to' discuss  them 
first  before  the  action  of  other  drugs  be  considered, 
especially  as  observers  differ,  more  or  less,  in  their 
results. 

Nasse,  it  has  been  said,  appears  to  have  been  the 
first  to  note  the  effect  of  calomel  in  a  dog  in  whom  a 
biliary  fistula  had  been  set  up.  The  observations  were 
made  in  the  month  of  November,  the  dog  being  kept 
upon  the  same  food  throughout,  apparently  bread  and 
potatoes,  and  from  the  6th  to  the  15th  of  the  month, 
carbonate  of  soda  having  been  added  to  the  food.  From 
Nov.  24  to  27,  a  gramme  of  calomel  was  given  within 
36  hours  with  the  food.  The  first  day,  the  dog  left 
half  the  food  set  before  it ;  the  second,  at  mid-day, 
it  showed  no  appetite  ;  but  on  the  third  day  it  left 
nothing.  The  amount  of  bile  was  less  on  the  first  day, 
but  much  increased  on  the  two  following.  The  first 
night,  after  that  the  dog  had  taken  '75  grm.  of  calomel, 
the  amount  of  bile  secreted,  36*8  grammes,  was  of  a 
high  specific  gravity  (1015*7) .f  '^^'^^  mean  of  the  two 
last  days  was  2i2'55  fluid  bile,  and  4388  grm.  of  solid 
bile.  The  mean  of  eight  days  before  the  mercury  was 
I26"5  grm.  of  fluid  bile,  and  2*887  of  solid  bile  ;  so  that 
the  amount  both  of  fluid  and  solid  bile  would  seem  to 
be  increased. 

*  Nasse,  Commcntatio  dc  bills  quot'uiie  a  cane  sccreta  copia  ct  indole,  Marburg, 
1851,  p.  18  et  seq.  Those  who  wish  to  see  the  history  of  opinions  on  mercury  as  a 
cholagogue  may  consult  Dr.  Fraser's  article  in  the  Edinburgh  Medical  jfourual, 
April,  1871,  vol.  xvi.  p.  904. 

f  Nasse,  op.  cit.  p.  11. 


Dr.  ScoWs  Observations.  159 

Kolliker  and  Miiller  gave  four  grains  of  calomel  to 
one  of  their  dogs,  at  10  a.m.  on  the  26th  day  after  the 
biliary  fistula  had  been  set  up.  Five  observations  in 
the  afternoon  gave  as  a  mean  for  every  half  hour  3 "823 
gr.  which  was  not  much  over  the  ordinary  average. 
The  next  day,  four  observations  gave  3*267  gr.  as 
mean,  which  was  therefore  somewhat  less  than  cus- 
tomary. On  the  2ist  and  29th  days,  the  dog  was 
again  given  four  grains  of  calomel ;  but  the  mean  of 
seven  observations  gave  only  2 '183  for  every  half  hour. 
The  bile  also  became  brownish  and  thick  so  that  it 
would  hardly  flow.  But  it  should  be  noted  that  the 
dog's  health  was  bad ;  it  was  losing  weight,  and 
had  diarrhoea;  the  stools  were  not  green  but  grey ; 
later  on  they  were  bloody.  For  some  days  the  dog 
would  only  take  bread  and  milk.* 

Dr.  George  Scott,  in  1858,  in  Dr.  Lionel  Beale's 
laboratory,  set  up  a  biliary  fistula  in  a  dog ;  he  calcu- 
lated the  amount  of  fluid  bile  and  solid  bile  secreted  in 
24  hours,  for  two  days,  before  calomel  was  given  ;  and 
also  the  average  amount  secreted  in  24  hours,  for  two 
days,  after  the  calomel  was  given.  He  thought  that 
the  action  of  the  calomel  would  last  longer  than  24 
hours.  The  bile  was  collected  twice  a  day,  morning 
and  evening.  The  calomel  was  given  each  time  after 
the  morning's  bile  was  collected,  and  therefore  the 
effect  of  medicine  would  be  upon  the  bile  of  the  day 
following.  There  were  four  trials  of  the  calomel ;  and 
all  four  gave,  in  Dr.  Scott's  opinion,  but  one  result, 
"a  diminution  in  the  amount  of  fluid  bile  and  bile- 
solids  secreted  after  the  administration  of  large  doses  of 
calomel."t 

The  details  of  the  experiments  made  by  Dr.  Scott 'are 

*  Kolliker  and  Miiller,  Verhandlungen  der  phys.-med.  Gesellschaft  in  Wurzburg, 
1855.  Bd.v.  p.  231. 
f  George  Scott,  Beale's  Archives  of  Medicine,  1859,  vol.  i.  p.  209. 


i6o  Mercury  as  Cholagogue. 

as  follows :  i.  The  average  amount  of  bile  secreted  in 
24  hours  on  June  nth  and  June  13th,  was  19607  grains 
of  fluid  bile  ;  104*438  grains  of  solid  bile  ;  and  32*864 
grains  of  bile  acids.  Three  grains  of  calomel  were 
given  at  3  o'clock  in  the  afternoon  of  June  13th.  The 
average  of  the  two  days  after  giving  this  dose  was 
1358*1  grains  of  fluid  bile;  70*4  grains  of  solid  bile, 
and  26*2  grains  of  bile  acids.  Less  food  was,  however, 
taken  after  the  calomel. 

ii.  The  bile  of  24  hours  collected  on  June  i6th  was 
1639*9  grains  in  weight:  solid  bile,  77*599  grains  ;  the 
bile  acids,  12*5  grains.  On  this  day  six  grains  of  calo- 
mel were  given  at  half  past  eleven  in  the  morning ;  the 
bile  collected  on  June  17th  was  518*7  grains  in  weight; 
solid  bile,  42*18  grains  :  the  bile  acids  10*4  grains.  No 
food,  however,  but  12  ounces  of  milk  was  taken  on 
June  17th,  and  only  9  ounces  of  water  on  June  i8th, 
yet  the  amount  of  bile  collected  on  June  19th  was 
Siy°y  grains  of  fluid  bile;  61*7  grains  of  solid  bile; 
and  27*486  grains  of  the  bile  acids.  Thus  it  would 
seem  that  merely  withholding  food  would  not  cause 
such  a  great  decrease  as  was  seen  after  the  calomel. 

iii.  On  the  2nd  and  3rd  of  July,  the  average  quantity 
of  bile  for  24  hours  was  3044*8  grains  of  fluid  bile  ; 
139*2  grains  of  solid  bile,  and  61  *g  grains  of  bile  acids. 
The  third  dose  of  calomel,  10  grains  in  amount,  was 
given  at  half  past  four  on  July  3rd.  The  average  for 
24  hours  of  the  bile  passed  on  July  4th  and  5th  was 
2720*9  grains  of  fluid  bile  ;  135*4  grains  of  solid  bile  ; 
and  70*6  grains  of  the  bile  acids.  The  bile  acids,  it 
should  be  noted,  were  thus  increased. 

iv.  On  the  6th  and  7th  of  July,  the  average  quantity 
of  bile  for  24  hours  was  2658*6  grains  of  fluid  bile  ; 
1 17.7  grains  of  solid  bile;  57*4  grains  of  bile  acids. 
Twelve  grains  of  calomel  were  given  at  six  o'clock  in 
the  afternoon  of  July  7th.      The   average  of  July  8th 


Observations  of  the  Edinburgh  Committee.         i6i 

and  gth  for  24  hours  was  1728*9  grains  of  fluid  bile ; 
85-6  grains  of  solid  bile  ;  and  45-9  grains  of  the  bile 
acids. 

The  Edinburgh  Committee  praise  Dr.  Scott  for  the 
careful  and  scientific  way  in  which  he  has  made  these 
experiments,  and  I  think  every  one  who  is  able  to  judge 
of  these  matters  will  more  than  agree  with  them  on  this 
point.  They,  however,  look  upon  Dr.  Scott's  observa- 
tions as  valuable  contributions  to  the  study  of  the  influ.- 
ence  of  calomel  on  the  bile  rather  than  data  which  in 
themselves  warrant  any  conclusion.  They  think  that 
the  diminution  of  the  bile  is  not  nearly  so  great  as 
Dr.  Scott  would  make  out. 

The  Edinburgh  Committee,  appointed  by  the  British 
Association  for  the  Advancement  of  Science  to  investi- 
gate the  action  of  mercury  on  the  bile,  began  their  work 
by  questioning  if  mercury  have  the  same  action  on  dogs 
as  on  man.  The  injection  of  corrosive  sublimate  under 
the  skin  of  dogs  brought  out  the  same  symptoms  as  in 
man  ;  salivation,  discharge  of  mucus  from  the  nostrils, 
foetid  breath,  and  ulceration  of  the  gums.  All  these 
symptorns  appeared  whether  a  biliary  fistula  had  or  had 
not  been  established.  In  all  the  dogs  without  a  biliary 
fistula  profuse  diarrhoea  was  caused.  In  the  dogs  with 
biliary  fistula,  diarrhoea  was  slight  in  one  and  entirely 
absent  in  the  other  two.  The  Committee  conclude  that 
the  action  of  mercury  on  the  dog  is  the  same  as  that  on 
man. 

Their  next  experiments  were  on  the  action  of  blue 
pill.  In  one  dog,  the  mean  amount  of  bile  escaping 
from  a  biliary  fistula  in  24  hours  from  June  nth  to 
June  igth  was  ii9'76  grammes,  of  which  7'622  grammes 
were  bile  solids  and  i'259  gramme  inorganic  salts;* 
from  June  2gth  to  July  4th,  the  mean  was  131 '31 
grammes,   of  which   4"7i    grammes    were    bile    solids ; 

*  By  inorganic  salts  is  meant  the  residue  left  after  incineration  of  the  bile. 

M 


1 62  Observations  on  Mercury  as  a 

and  1*343  gramme  inorganic  salts.  From  July  gth  to 
July  17th  5  grains  of  blue  pill  were  given  daily,  and 
the  mean  for  24  hours  during  this  time  was  127*6 
grammes  of  fluid  bile,  of  which  5-16  grammes  were 
solids,  and  1*38  gramme  inorganic  salts.  Another 
series  of  observations  was  made,  but  accidents  ren- 
dered it  valueless. 

Much  the  same  results  were  attained  with  calomel. 
During  7  days  from  Sept.  21st  to  Sept.  27th  the  mean 
of  fluid  bile  flowing  from  a  fistula  was  82*46  grammes, 
of  which  5*31  grammes  were  solids,  and  1.042  gramme 
inorganic  salts.  From  Sept.  28th  to  Oct.  3rd,  calomel 
was  given  to  the  dog  in  doses  of  two  grains,  once, 
twice,  or  three  times  a  day.  The  mean  of  fluid  bile 
during  the  first  four  days  was  60*02  grammes.  The 
efl'ect  of  the  calomel  on  the  health  of  the  dog  was  very 
decided,  and  it  died  on  Oct.  5th. 

It  was  then  determined  to  note  the  effect  of  small 
doses  of  calomel  frequently  repeated.  The  mean  of 
four  days  before  the  calomel  was  given  was  70*62 
grammes  of  fluid  bile  ;  of  which  3*792  grammes  were 
solids,  and  083  gramme  inorganic  salts.  On  Oct.  30th 
seven  pills  were  given  ;  each  pill  held  jV  grain  of  calo- 
mel. An  hour  passed  between  the  giving  of  each  pill. 
In  the  same  way  14  pills  were  given  on  Nov.  ist,  and 
6  pills  on  Nov.  2nd.  The  calomel  rapidly  acted  on  the 
health,  and  the  dog  died  on  Nov.  3,  food  having  been 
refused  for  three  days  before.  But  no  change  in  the 
amount  of  bile  was  seen  :  the  mean  of  the  four  days 
after  the  calomel  was  almost  the  same  as  the  mean  of 
the  four  days  before  :  70*32  grammes  of  fluid  bile, 
3-732  of  solids,  and  0*89  gramme  of  inorganic  salts. 

Another  experiment  was  made  with  calomel  in  doses 
large  enough  to  cause  purging.  The  average  of  six 
days  before  the  calomel  was  given  was  357*4  grammes 
of  fluid  bile,  13*11  grammes  of  solids,  and  3*12  grammes 


Cholagogue  by  the  Edinburgh  Committee.  163 

of  bile  salts.  Ten  grains  of  blue  pill  were  then  given 
to  the  dog,  and  the  three  following  days  ten  grains  of 
calomel  were  given  daily.  The  two  first  doses  of  mer- 
cury caused  slight  purging ;  the  two  last  caused  marked 
purging.  During  these  four  days  there  was  an  un- 
doubted decrease  of  the  amount  of  bile.  The  mean 
was  272*67  grammes  of  fluid  bile  ;  778  grammes  of 
solids  ;  and  2"o6  grammes  of  inorganic  salts.  The 
health  of  the  animal  was  unaffected  by  the  purging. 

Some  experiments  were  also  made  with  corrosive 
sublimate.  The  mean,  during  three  days  before  the 
corrosive  sublimate  was  given,  was  105*4  grammes  of 
fluid  bile  ;  4*144  grammes  of  solids  ;  and  '948  gramme 
of  inorganic  salts.  On  the  4th  day,  two  doses,  of 
f  grain  of  corrosive  sublimate  were  injected  under  the 
skin  of  the  dog,  the  first  at  i  p.m.,  the  second  at  g 
a.m.  the  next  day.  The  bile  secreted  in  the  24  hours 
under  the  influence  of  this  corrosive  sublimate  was  78 
grammes  ;  the  bile  solids  were  3*178  grammes  and  the 
inorganic  salts  '717  gramme.  The  dog  died  during 
the  night  after  the  second  dose,  having  shown  general 
tremor,  purging  with  bloody  fluid  stools,  and  discharge 
from  the  nose". 

The  next  trial  was  with  smaller  doses.  The  mean  of 
three  days  was  127*15  grammes  of  fluid  bile;  6*43 
grammes  of  solids,  and  i"03  gramme  of  inorganic  salts. 
For  ten  days  corrosive  sublimate  was  injected  under  the 
skin  ;  the  first  three  days  ^  grain  in  single  doses  daily ; 
the  remaining  seven  days,  twice  daily,  save  that  the 
last  dose  injected  was  ^  grain.  The  mean  during 
these  ten  days  was  of  fluid  bile,  113*8  grammes;  of 
solids,  5*972  grammes ;  and  of  inorganic  salts,  '99 
gramme.  The  health  of  the  animal  did  not  suffer  and 
its  weight  continued  the  same.  J  grain  was  given 
twice  on  the  nth  day  and  once  on  the  12th,  and  obser- 
vations were  suspended  as  the  dog  was  then  suffering 

M  2 


164  Observations  on  Mercury 

much  from  the  effects  of  the  drug.  The  fluid  bile  fell 
to  a  fourth,  and  the  bile-solids  to  a  third,  of  what  they 
had  been  the  day  before. 

Another  experiment  of  the  same  kind  was  carried  out 
with  results  very  much  the  same. 

The  Committee  conclude  that  blue  pill,  calomel,  and 
corrosive  sublimate,  "when  given  to  dogs  in  either 
small,  gradually  augmented,  or  in  large  doses,  do  not 
increase  the  biliary  secretion  ;  they  do  not  even  influ- 
ence it  so  long  as  neither  purgation  nor  impairment  of 
health  are  {sic)  produced,  but  they  diminish  it  as  soon 
as  they  do  either  or  both."* 

Up  to  this  point,  the  experiments  which  have  been 
spoken  of  have  been  made  on  the  following  plan  :  a 
biliary  fistula  has  been  set  up,  and  after  the  dog  had 
regained  its  health,  the  amount  of  bile  passed  in  24 
hours  has  been  collected,  in  various  ways,  that  used  by 
Dr.  Scott  being  the  most  accurate,  and  a  mean  struck, 
believed  to  represent  that  of  health  :  the  drug  to  be 
tested,  in  most  cases  mercury,  was  then  given  ;  and 
the  amount  of  bile  passed,  day  by  day,  measured  and 
compared  with  that  given  before  the  drug.  The. ex- 
periments of  Rohrig  and  Dr.  Rutherford  have  all  been 
made  somewhat  differently. 

In  Rohrig's  plan,  the  dogs  and  rabbits  were  made 
motionless  by  woorara,  and  artificial  respiration  set  up. 
This  last  was  carried  on  with  the  greatest  regularity,  as 
it  was  found  that  slight  changes  in  the  breathing  led 
also  to  changes  in  the  manner  of  expulsion  of  the  bile. 
A  glass  cannula  was  then  inserted  into  the  common 
duct,  the  gall-bladder  pressed  upon  so  as  to  fill  the 
cannula  with  bile,  and  the  cystic  duct  clamped  to  pre- 
vent the  return  of  bile   into  the  gall-bladder.      In  this 

*  Edinburgh  Committee,  Report  of  the  Thirty-eighth  Meeting  of  the  British 
Association  for  the  Advancement  of  Science ;  held  at  Norwich  in  August,  1868. 
London,  1869,  p.  222. 


by  Rohrig  and  Dr.  Rutherford.  165 

way  all  the  bile  which  passed  down  the  hepatic  duct 
escaped  at  the  end  of  the  cannula,  and  the  quickness  or 
slowness  ot  the  secretion  was  judged  of  by  counting  the 
seconds  between  the  fall  of  each  drop  of  bile  from  the 
end  of  the  cannula. 

Rohrig  says,  that  with  large  doses  of  calomel  (20 
grains  for  a  dog)  it  is  sometimes,  but  rarely,  seen  that 
the  bile  will  again  begin  to  flow  after  it  have  completely 
stopped ;  and  that  the  drug  is  able  to  increase  the 
secretion,  after  a  certain  fashion,  if  it  have  only  fallen 
off  in  amount.  He  speaks  of  two  cases  in  which  the 
secretion  had  completely  left  off;  20  grains  of  calomel 
in  emulsion  were  then  given  ;  and  in  two  hours  the  bile 
had  again  begun  to  flow  at  the  rate  of  one  drop  for 
every  120  or  130  strokes  of  the  metronome  ;  at  the 
end  of  another  hour,  there  was  one  drop  in  85  or  79 
strokes ;  but  in  half  an  hour's  time  the  secretion  be- 
came less,  and  in  35  minutes  had  altogether  stopped. 
Calomel  may  be  more  trusted  if  it  be  desired  only  to  in- 
crease a  flow  of  bile  which  has  not  entirely  ceased;  and 
in  this  respect  the  drug  gives  much  the  same  results 
as  sulphate  of  magnesia,  which,  according  to  Rohrig, 
acts  feebly  on  the  secretion  of  bile  ;  but  his  single  ex- 
periment on  this  point  does  not  seem  to  me  worthy  of 
very  great  attention.* 

Dr.  Rutherford  modified  Rohrig's  process  so  far  that 
the  amount  of  secretion  was  not  measured  by  the  time 
that  passed  between  the  fall  of  each  drop  but  by  the 
amount  of  secretion  itself,  received  in  a  finely  gradu- 
ated tube.  The  trials  were  always  made  on  dogs 
which  had  fasted  for  18  hours,  and  which  were  motion- 
less with  woorara.f  Several  experiments  were  made 
with  mercurial  salts.     Ten  grains  of  calomel  in  7  C.C. 

*  Rohrig,  Strieker's  Medizinische  yahrbilcher,  Wien,  1873,  p.  254. 
f  Rutherford  and  Vignal,  Experiinents  on  the  Biliary  Secretion  of  the  Dog,  p.  i. 
Report  attached  to  the  British  Medical  jfournal,  1875,  vol.  ii. 


1 66  Mercury  as  Cholagogue. 

of  water  were  injected  into  the  duodenum  of  a  dog 
weighing  ig'i  kilogrammes,  and  an  increase  of  the  biHary 
secretion  followed.  For.  two  hours  before  the  calomel, 
the  amount  of  bile  secreted  was  3*35  C.C,  in  two  hours 
immediately  after,  it  was  4*25  C.C.  After  a  second 
dose  of  ten  grains  of  calomel,  the  secretion  again  rose 
to  4*72  C.C.  in  two  hours.  In  three  other  experiments 
with  calomel,  no  increase  was  seen  ;  in  one,  there  was 
a  decrease  ;  in  the  second,  no  increase ;  in  the  third, 
three  grains  only  were  given  ;  and  in  three-quarters  of 
an  hour  after  the  first  dose,  an  increase  took  place  ;  but 
the  value  of  this  increase  is  doubtful,  as  quite  as  great 
an  increase  had  taken  place  before  the  calomel  was 
given.  Two  more  doses  of  three  grains  were  given, 
and  were  followed  by  a  decrease  of  the  amount  of  the 
bile  and  of  the  percentage  of  solids.* 

Later  on  in  the  series  of  experiments,  the  calomel 
was  given  mixed  with  bile.  Calomel  is  said  to  be 
slightly  soluble  in  this  humour ;  and  it  might  be  as- 
serted that,  owing  to  the  absence  of  bile  from  the  intes- 
tines, the  calomel  could  no  longer  act,  as  it  had  no 
longer  a  solvent.  In  two  experiments  the  calomel,  even 
when  mixed  with  bile,  and  placed  in  the  duodenum,  did 
not  increase  the  amount  of  bile. 

It  was  suggested  to  Professor  Rutherford  that,  the 
calomel  being  introduced  into  the  duodenum,  the  action 
of  the  gastric  juice  was  avoided  ;  and  that  the  action  of 
the  gastric  juice  might  be  to  convert  the  calomel  into 
corrosive  sublimate.  It  was  found,  in  fact,  that  five 
grains  of  calomel,  if  digested  for  17  hours  in  a  2  per 
mille  solution  of  hydrochloric  acid,  at  the  temperature 
of  the  human  stomach,  would  yield  ^  grain  of  corro- 
sive sublimate.  Some  experiments  were  accordingly 
made  with  corrosive  sublimate.  In  the  first,  a  dog, 
weighing  8'8  kilogrammes,  had  ^^^  grain,  3^,  J^,  J^,  tV, 

*  Rutherford  and  Vignal,  op.  cit,  p.  14. 


Dr.  RtUherford' s  Experiments.  167 

^o  grain  of  corrosive  sublimate,  dissolved  in  3  C.C.  of 
water,  injected  into  the  duodenum  at  intervals.  Alto- 
gether f  grain  were  given.  A  slight  increase  followed 
the  fourth  dose  ;  but  the  result  of  the  whole  experiment 
may  be  looked  upon  as  negative.  But  in  the  next  two 
experiments  quite  a  different  result  appeared.  A  little 
bile  was  added  to  the  solution  of  corrosive  sublimate. 
After  the  injection  of  this  body,  in  yV  grain  doses, 
into  the  duodenum  of  dogs  weighing  16  and  17  kilo- 
grammes, the  amount  of  bile  secreted  rose  to  a  surpris- 
ing height,  from  -17  or  '20  the  kilogramme  of  weight, 
to  '47  or  "55  the  kilogramme.  Two  more  experiments 
were  made  with  a  mixture  of  corrosive  sublimate  and 
calomel  in  bile.  In  the  first  of  these  there  was  some 
increase,  and  in  the  second,  an  immense  rise  in  the 
quantity  of  bile  secreted.  A  final  experiment  with  cor- 
rosive sublimate  alone  was  made  ;  but  the  results,  from 
the  great  variations  of  the  amount,  whether  corrosive 
sublimate  were  given  or  not,  cannot  be  looked  upon  as 
proving  much.* 

Seeing,  then,  that  corrosive  sublimate  has  a  decided 
action  on  the  secretion  of  bile,  and  that  some  part  at 
all  events,  of  calomel,  exposed  to  the  action  of  hydro- 
chloric acid  of  the  same  strength  as  the  gastric  juice,  is 
turned  into  corrosive  sublimate,  it  becomes  a  matter  of 
speculation  whether  calomel  might  not,  if  introduced 
into  the  stomach,  act  on  the  liver  by  a  partial  conver- 
sion into  corrosive  sublimate.  And  I  fear  I  must  here 
state  my  belief  that  I  do  not  think  this  question  has 
been  completely  answered.  Dr.  Rutherford  injected 
through  the  gastric  wall  of  a  dog  five  grains  of  calomel, 
and  says  "the  result  of  the  experiment  was  entirely 
negative,  both  as  regards  the  liver  and  intestinal 
glands,"    that  is,   no  purgative  action  was   caused   by 

*  Rutherford  and  Vignal,  op.  cit.  p.  79,  attached  to  the  British  Med.  jfournal 
for  July  7,  1877. 


1 68  Drugs  which  have  no  Apparent 

the  calomel.  It  will  be  admitted  on  all  hands  that 
calomel  commonly  has  a  purgative  action  ;  but  if  no 
purging  was  caused  in  this  case,  why  should  the 
effect  on  the  liver,  if  any,  be  seen  ?  After  the  death  of 
of  the  dog,  the  calomel  was  found  "apparently  un- 
changed, enveloped  in  the  mucus  of  the  stomach."  I 
am  informed  that,  in  the  present  state  of  chemistry, 
the  estimation  of  mercurial  salts  in  organic  fluids 
is  attended  with  extraordinary  difficulties,  and  Dr. 
Rutherford  does  not  seem  to  have  attempted  an  es- 
timation of  this  sort.  But  until  this  shall  have  been 
done,  I  think  it  will  hardly  be  possible  to  deny  posi- 
tively that  the  action  of  calomel  is  not  accompanied  by 
some  change  in  its  chemical  properties.* 

Leaving  now  the  discussion  of  the  action  of  mercury 
as  a  cholagogue,  unsatisfactory  as  this  may  seem,  the 
influence  of  other  drugs  upon  the  secretion  of  the  bile 
will  be  considered.  It  will  be  convenient  to  take 
these  medicines  in  some  order ;  and  the  results  of 
Dr.  Rutherford's  observations  will  be  followed  as  a 
guide ;  not  only  because  he  has  made  trial  of  a  far 
larger  number  of  drugs  than  any  other  observer,  but 
because  his  results,  from  the  great  care  and  improved 
methods  employed,  are  more  worthy  of  attention  than 
those  of  any  who  have  gone  before  him. 

i.  The  bodies  which  have  no  apparent  action  upon 
the  secretion  of  bile  are  the  following  : 

Morphia  Dilute  Alcohol 

Hyoscyamus  Bicarbonate  of  Soda 

Atropia  Iodide  of  Potassium 
Tannic  Acid 

Morphia. — Rohrig  injected  i"6  C.C.  of  tinctura  the- 
baica  into  the  jugular  vein  of  a  dog ;    the  secretion  of 

*  See  a  very  interesting  research  by  Carl  Voit  on  the  manner  in  which  the 
insoluble  calomel  is  absorbed  and  acts.  {Phys.-chcm.  Untersucluoigcn,  Augsburg, 
1857,  p.  49.) 


Action  as  Cholagogues.  169 

bile  had  fallen  to  one  drop  in  62  seconds,  as  the  dog 
had  been  two  hours  under  observation,  and  was  very 
weak.  Nevertheless,  the  secretion  began  at  once  to 
rise,  and  in  twenty  minutes  was  one  drop  in  26  seconds. 
A  like  rise  was  seen  after  the  injection  of  4.8  C.C.  into 
the  bowel.*  Dr.  Rutherford  came  to  the  conclusion 
that  three  grains  of  morphia,  injected  into  the  bowel 
had  no  influence  on  the  secretion  of  bile. 

Hyoscyamus  also  has  no  noteworthy  effect  on  the 
secretion  of  bile. 

Neither  of  these  bodies  interferes  with  the  action  of  a 
cholagogue  like  salicylate  of  soda ;  when  the  salicylate 
was  given  after  morphia  or  hyoscyamus,  the  secretion 
of  bile  rose  at  once  to  as  high  a  point  as  if  no  morphia 
or  hyoscyamus  had  been  given. f 

Atropia.  It  is  believed  by  practitioners  that  bella- 
donna decreases  the  secretion  of  the  milk  and  sweat. 
Dr.  Rutherford  therefore  thought  it  well  worth  while  to 
test  its  action  on  the  bile.  It  was  found,  however,  to 
have  no  immediate  action,  neither  increasing  nor  de- 
creasing the  secretion  ;  and  the  same  result  was  at- 
tained by  Laffter,  in  Heidenhain's  laboratory,  before  the 
year  1873. J  But  as  atropia  antagonises  the  action  of 
calabar  bean  in  other  parts,  so  it  antagonises  its  action 
on  the  liver  ;  calabar  bean  increasing  the  amount  of 
bile  as  well  as  of  the  saliva,  tears  and  succus  entericus.^ 

Carbonate  of  Soda  early  attracted  notice  ;  from  the 
same  reason,  apparently,  that  mercury  did:  it  had  been 
found  useful  in  the  bilious  state,  that  is,  acute  or  chronic 
gastric  catarrh,  and  so,  by  a  natural  blunder,  connect- 
ing bilious  disorders  with  the  bile,  carbonate  of  soda 
was  thought  to   have  some  special  action  on  the  bile. 

*  Rolirig,  op.  cit.  p.  272. 

f  Rutherford,  British  Medical  journal,  1879,  vol.  i.  p.  135. 

X  Th.  Laffter,  Versuche  zur  Physiologic  der  Gallcnsecrction,  Diss.  Inaug.  Bres- 
lau,  1873,  p.  22.     He  came  to  no  trustworthy  results  with  calabar  bean. 
§  Rutherford,  British  Med.  journal,  1878,  vol.  ii.  pp.  S61  and  909. 


170  Drugs  which  Decrease  the 

Hermann  Nasse  added  on  the  first  day  to  the  food  of 
the  dog  on  whom  he  had  made  a  bihary  fistula  2'5 
grammes  (37  grains)  of  carbonate  of  soda.  On  the 
third  and  fourth  days,  1-25  gramme  (about  18  grains) 
was  given.  On  the  three  following  days  the  food  and 
carbonate  of  soda  were  increased  by  one  half.  During 
the  first  days  when  the  large  doses  were  given,  the 
amount  both  of  fluid  and  solid  bile  was  much  de- 
creased.* Rohrig  also  finds  that  carbonate  of  soda 
causes  a  decrease  for  several  hours  of  the  amount 
of  bile  secreted  both  in  rabbits  and  dogs.f  Dr. 
Rutherford,  on  the  other  hand,  found  that  bicarbon- 
ate of  soda  feebly  increased  the  amount  of  bile  se- 
creted. In  his  two  experiments  the  amount  of  bile 
slightly  rose  after  each  dose.  J 

ii.  It  was  formerly  thought  that  the  drugs  which 
caused  purging  would  also  increase  the  secretion  of 
bile,  probably  because  it  was  believed  that  unchanged 
bile  appeared  in  the  stools.  An  ingenious  anonymous 
writer§  explains  the  good  effects  of  purging  by  the 
following  hypothesis :  the  bile,  if  we  follow  Schiff's 
observations,  is  continually  making  a  circulation  be- 
tween the  liver  and  the  intestines  :  first  being  poured 
into  the  duodenum,  then  absorbed  from  the  intestines 
into  the  blood,  then  carried  by  the  blood  to  the  liver 
again,  and  by  this  organ  again  excreted  into  the 
duodenum :  purgatives  act  by  breaking  this  vicious 
circle  ;  they  hurry  the  bile  through  the  intestines,  not 
letting  it  rest  long  enough  in  the  intestine  to  be  ab- 
sorbed, and  so  the  patient  is  relieved  from  the  excess 
of  bile. 

It  was  stated  by  Rohrig  that  purging  by  itself 
increased   the    amount    of  bile    ;||  but  the   Edinburgh 

»  H.  Nasse,  op.  cit.  p.  g.  f  Rohrig,  op.  cit.  p.  271. 

X  Rutherford,  British  Med.  youvnal,  1879,  vol.  i.  p.  105. 

§  Probably  Dr.  Lauder  Brunton,  British  Med.  jfotinial,  1873,  vol.  i.  p.  15. 

II  Rohrig,  op.  cit.  p.  249. 


A  mount  of  Bile  Secreted.  171 

Committee*  and  Dr  Rutherford§  came  to  the  opposite 
conclusion  ;  and  in  this  matter,  as  in  many  others,  I 
should  be  inclined  to  accept  their  results  rather  than 
those  of  Rohrig.  The  drugs,  which  increase  the 
intestinal  fluid,  but  have  no  action  on  the  bile,  are : 

Calomel  Castor  Oil 

Gamboge  Chloride  of  Ammonia 

Sulphate  of  Mag^nesia  Menispermin 
Sulphate  of  Manganese 

Sulphate  of  Magnesia.  This  salt  is  said  by  Rohrig 
to  have  a  slight  influence  on  the  bile,  raising  the  secre- 
tion from  one  drop  in  98  seconds  to  one  in  34. J  Dr. 
Rutherford,  however,  finds  that  sulphate  of  magnesia 
has  no  action  as  a  cholagogue,  but  that  the  secretion 
of  bile  is  diminished  when  purging  comes  on.§ 

Castor  Oil.  RohrigH  and  Rutherford^  agree  that 
Castor  oil  is  almost  without  influence  upon  the  amount 
of  bile  secreted. 

iii.  The  only  body  the  primary  action  of  which  is 
known  to  cause  a  decreased  secretion  of  bile  is  : 

Acetate  of  Lead.  Both  Rohrig  and  Dr,  Rutherford  hold 
that  this  has  a  direct  depressing  efl"ect  upon  the  secre- 
tion of  bile.  In  Rohrig's  hands  it  was  noted  that  when 
acetate  of  lead  was  injected  into  the  intestine  of  a  dog 
the  secretion  fell  from  one  drop  in  21  seconds  to  one  in 
50  or  more.**  Dr.  Rutherford  injected  fifty  grains  of 
acetate  of  lead,  in  doses  of  ten  grains  each,  into  the 
duodenum  of  a  dog  and  found  a  decided  fall  after  every 
dose.  The  fall  was  not  due  to  the  liver  being  ex- 
hausted ;  for  a  dose  of  salicylate  of  soda  caused  the 
amount  of  bile  to  rise  to  a  point  higher  than  it  was  at 
the  beginning  of  the  experiment. "ff 

*  Edinburgh  Committee,  op.  cit.  229.     f  Rutherford  and  Vignal,  op,  cit.  p.  17. 
+  Rohng,  op.  cit.  p.  254.  §  Rutherford  and  Vignal,  op.  cit.  p.  73. 

II  Rohrig,  op.  cit.  p.  255.  IT  Rutherford  and  Vignal,  op.  cit.  p.  16. 

**  Rohrig,  op.  cit.  p.  270. 
ft  Rutherford,  Brit.  Med.  journal,  1878,  vol.  ii.  p.  945. 


172  Drugs  which  Feebly  Raise 

iv.  The  following  drugs  are  able  feebly  to  raise  the 
secretion  of  bile  : 

Croton  Oil  Chloride  of  Sodium 

Senna  Bicarbonate  of  Potash 

Taraxacum  Jaborandi 

Scammony 
Croton  oil.  Rohrig  held  croton  oil  to  be  one  of  the 
most  active  cholagogues  ;  and  it  stands  at  the  head  of  his 
list.  A  "teaspoonful,"  diluted  with  olive  oil  and  thrown 
into  the  duodenum,  called  forth  in  an  hour  and  a  half 
an  active  secretion  of  bile,  so  that  one  drop  fell  from 
the  cannula  every  three  seconds.  In  other  experiments 
the  bile  was  very  viscid  and  the  drops  could  not  be 
counted.*  With  smaller  doses,  Dr.  Rutherford  found 
different  appearances.  After  fifteen  grains  of  croton  oil 
(about  30  drops,)  diluted  with  sixty  minims  of  almond 
oil,  were  injected,  a  fall  took  place  ;  with  six  grains, 
no  decrease  or  increase  ;  with  three  grains,  a  decided 
increase. t 

Senna  was  found  by  Rohrig  to  have  an  active  effect 
on  the  secretion  of  bile.  After  a  dose  of  15  grammes 
in  150  C.C.  of  fluid,  the  bile,  from  dropping  once  in 
every  60  seconds  began  in  an  hour  to  drop  once  in  4  to 
5,  although  this  great  rapidity  lasted  but  a  short  time 
and  was  followed  later  on  by  complete  stopping  of  the 
secretion. J  Dr.  Rutherford,  however,  found  very  little 
change  in  the  secretion  before  and  after  the  giving  of 
senna  in  three  experiments  ;  and  if  any,  the  bile  con- 
tained less  solids. § 

Taraxacum.  This  drug  was  found  by  the  Edinburgh 
Committee  to  be  tolerably  inert.  They  report  that 
doses  of  the  solid  extract  varying  from  60  to  240  grains 
had  no  influence  upon  the  bile  nor  the  health  of  the 
dogs;  nor  did  they  cause  purging. ||  Dr.  Rutherford's 
further  experiments  agree  with  this  statement.^ 

*  Rohrig,  op.cit.  p.  250.  t  Rutherford  and  Vignal,  op.  cit.  p.  3. 

X  Rohrig,  op.  cit.  p.  254.  §  Rutherford  and  Vignal,  op.  cit.  p.  10. 

II  Edinburgh  Committee,  op.  cit.  p.  229.  IT  Rutherford  and  Vignal,  op.  cit.  p.  13. 


the  Amount  of  Bile  Secreted.  173 

Chloride  of  Sodium.  Dr.  Rutherford  made  only  one 
experiment  with  this  drug,  four  doses  of  120  grains 
each  being  injected  into  the  duodenum.  The  amount 
of  bile  was  very  feebly  increased.* 

V.  The  following  are  the  bodies  which  markedly 
increase  the  secretion  of  bile  : 

Aloes  Corrosive  Sublimate 

Podophyllin  Muscarin 

Rhubarb  Nicotin 

Colchicum  Calabar  Bean 

Colocynth  Euonymin 

Jalap  Sanguinarin 

Ipecacuanha  Iridin 

Benzoates  Leptandria 

Salicylates  Baptisin 

Sulphates  of  Soda  and  Potash  Phytolaccin 
Phosphates  of  Soda  and  Ammonia       Hydrastin 

Dilute  Nitrohydrochloric  Acid  Juglandin 

Aloes.  After  mercury,  the  preparations  of  aloes  have 
received  most  attention  from  different  observers.  Kol- 
liker  and  Miiller  gave  one  of  their  dogs  one  grain  of 
extract  of  aloes  on  one  day,  and  two  grains  on  the 
following,  but  they  hardly  noted  any  change  in  the 
amount  of  bile  daily  secreted. f  Rohrig  tested,  with  his 
method,  the  action  of  aloes  on  a  dog  and  a  rabbit. 
No  details  are  given  of  the  experiment  on  the  dog,  in 
which  the  action  of  aloes  is  said  to  resemble  that  of 
jalap.  In  a  rabbit,  3  grammes  of  aloes  dissolved  in 
7'5  grammes  of  water  were  injected  into  the  small  in- 
testine. In  70  minutes,  the  secretion  of  bile,  which 
had  ceased  before  the  solution  of  aloes  was  given,  be- 
gan again,  79  to  77  seconds  passing  between  the  fall  of 
each  drop  ;  an  hour  after  this,  26  to  13  seconds  only 
between  each  drop  ;  in  a  short  time  the  secretion  began 
to  fall  off,  and  in  an  hour  had  completely  stopped. J 

*  Rutherford,  Brit.  Med.  yoimial,  1879,  vol.  i.  p.  71. 
f  Kolliker  and  Miiller,  op.  cit.  p.  231. 
X  Rohrig,  op.  cit.  p.  252. 


174  Drugs  which  Cause  a  Great 

Dr.  Rutherford  also  found  a  great  increase  of  bile, 
marked-  in  30  minutes  after  aloes  had  been  given. 
Though  the  bile  was  rendered  more  watery,  yet  a 
greater  amount  of  solids  was  excreted.  The  experi- 
ments were  made  on  two  dogs  into  whose  duodenum 
sixty  grains  of  aqueous  extract  of  Socotrine  aloes  in 
watery  solution  were  injected.* 

Podophyllin.  The  action  of  this  drug  upon  dogs 
with  biliary  fistulas  was  first  investigated  by  the  Edin- 
burgh Committee.  They  report  that  doses  of  podo- 
phyllin, varying  from  2  to  8  grains,  given  to  dogs, 
caused  a  decrease  of  the  solid  bile,  whether  purging 
came  on  or  not.  Doses  which  caused  purging  also 
caused  a  decrease  in  the  solid  and  fluid  parts  of  the 
bile.f  This  is  the  only  part  of  the  report  on  podo- 
phyllin which  coincides  with  the  experiments  made  by 
Dr.  Rutherford  later  on.  On  the  contrary,  he  found 
that  podophyllin  injected  into  the  duodenum  increased 
the  flow  of  bile  in  seven  experiments,  and  that  this  flow 
of  bile  is  greater  when  bile  also  is  present  in  the  duo- 
denurri.  The  mucous  membrane  of  the  intestine  was 
usually  much  reddened. J 

Rhubarb  was  found  by  Rohrig  to  raise  the  secretion 
of  bile  from  one  drop  in  every  92  seconds  to  as  much 
as  one  drop  in  every  9  seconds. §  Dr.  Rutherford  also 
found  rhubarb  a  remarkable  stimulant  to  the  secretion 
of  bile.  The  injection  of  rhubarb  into  the  duodenum 
was  always  followed  by  a  remarkable  rise  in  the  amount 
of  bile,  the  composition  of  which  remained  unchanged.^ 

Colocynth.  Rohrig  placed  colocynth  near  the  head  of 
his  list  ot  cholagogues ;  under  its  influence  he  saw 
that  a  drop  of  bile  fell  from  the  cannula  every  two  or 
three   seconds.*     Dr.    Rutherford  finds  that  colocynth 

*  Rutherford  and  Vignal,  op.  cit.  p.  7.     f  Edinburgh  Committee,  op.  cit.  p.  229. 
X  Rutherford  and  Vignal,  op.  cit.  p.  8.      §  Rohrig,  op.  cit.  p.  253. 
II  Rutherford  and  Vignal,  op.  cit.  p.  4.     %  Rohrig,  op.  cit.  p.  252. 


Increase  in  the  Amount  of  Bile.  175 

has  considerable  influence  in  increasing  the  secretion  of 
the  bile,  although  it  does  not  seem  to  be  worthy  of  the 
very  high  place  given  to  it  by  Rohrig.  Colocynth  in- 
creases both  the  fluid  and  solid  parts  of  the  bile.* 

Jalap.  Next  to  colocynth  as  a  cholagogue  Rohrig 
set  jalapt  and  Rutherford  agrees  with  him  that  the 
drug  is  a  considerable  stimulant  to  the  secretion  of  bile, 
though  its  chief  action  is  on  the  intestinal  glands.  J 

Benzoates  and  Salicylates.  The  study  of  the  physiolo- 
gical action  of  these  bodies  upon  the  liver  is  interest- 
ing. In  their  chemical  composition  they  are  allied. 
They  both  combine  with  glycocoll,  the  base  of  one  of 
the  bile  acids,  to  form  hippuric  and  salicyluric  acid. 

Benzoic  acid  has  been  long  employed  in  the  treat- 
ment of  jaundice,  and  it  was  made  the  subject  of  some 
experiments  by  Kiihne  about  twenty  years  ago.  He 
thought  that  in  jaundice  benzoic  acid  passed  out  by 
the  urine  unaltered  instead  of  combining  with  glycocoll 
to  pass  out  as  hippuric  acid.§  Kiihne's  theory  was, 
however,  soon  disproved,  as  the  presence  of  the  benzoic 
acid  in  the  urine  was  found  to  be  due  to  the  decom- 
position by  putrefaction  of  the  hippuric  acid.  It  is, 
therefore,  noteworthy  that  both  benzoates  and  sali- 
cylates greatly  increase  the  secretion  of  bile  by  the 
liver,  and  are  among  the  most  active  of  the  drugs  in- 
vestigated by  Dr.  Rutherford ;  and  his  results  on  this 
point  are  perhaps  the  most  interesting  to  the  physiolo- 
gist of  all  that  he  has  published.  Benzoic  acid,  itself, 
apparently  owing  to  its  insolubility,  has  but  sHght 
action  on  the  bile,  while  the  soda  and  ammonia  salts  at 
once  raise  the  amount  secreted. || 

Muscarin.     Prevost  says  that  a  few  milligrammes  of 

*  Rutherford  and  Vignal,  op.  cit.  p.  6g. 

f  Rohrig,  op.  cit.  p.  252. 

X  Rutherford  and  Vignal,  op.  cit.  p.  72. 

§  Kiihne,  Arch.  f. -path.  Anat.  1858,  Bd.  xiv.  p.  318. 

II  Rutherford,  British  Medical  jfotirnal,  1879,  vol.  i.  p.  6g. 


176 


Table  of  Cholagogues. 


muscarin  injected  into  a  vein  cause  a  notable  increase 
of  the  bile  in  a  dog.  Atropia,  however,  antagonises 
this  effect.* 

Nicotin.  Laffter  found,  in  Heidenhain's  laboratory, 
that  3  drops  of  nicotin  in  50  grammes  of  water,  injected 
into  the  jugular  vein  of  a  dog,  cause  an  immediate 
but  short  increase  of  the  bile.  This  appearance  was 
thought  due  to  the  contraction  of  the  ducts,  and  conse- 
quent expulsion  of  bile. f 

Euonymin,  Iridin,  etc.  The  eight  drugs  mentioned 
last  on  the  list  come  from  American  sources,  and  iridin 
and  euonymin  are  specially  active  in  increasing  the 
secretion  of  bile,  as  will  be  seen  by  the  following  table. 
This  table  has  been  borrowed  from  Dr.  Rutherford,  and 
he  remarks,  that  a  drug  may  be  looked  upon  as  a  power- 
ful cholagogue  if  it  raise  the  hourly  secretion  of  bile  for 
every  kilogramme  of  body  weight  to  0*4  C.C. 


Drug. 


Normal  secretion   of  bile  during  the 
influence  of  small  doses  of  woorara 

Podophyllin  .         . 

n  •  .  .  •  . 

Aloes     


Rhubarb 

Colchicum 

Euonymin 

J) 
Sanguinarin 

Iridin     . 


Leptandria    . 
Ipecacuanha 

>) 
Colocynth      , 


Dose  in 

Secretion  of 

Total  dose  in  grains. 

grains  for  ki- 
logramme of 

bile   for    kilo- 
gramme of 

body  weight. 

body- weight : 
an  hour. 

Before. 

After, 

C.C. 

C.C. 

0-35 

0-25 

0-15 

6  without  bile 

o-g 

0-04 

0-47 

4    with        „ 

0-23 

0-52 

I.OI 

60  without    ,, 

6-9 

0-34 

0-69 

60       „ 

I2-0 

0-26 

•Q3 

68       „ 

3-06 

0-17 

0-32 

60       ,,           „ 

2-5 

0-13 

0-4.5 

5    with        ,, 

0-26 

0-25 

0-47 

5          n 

0*21 

0-07 

0-46 

3       ,.           .. 

O'll 

o-i6 

0-30 

I       „ 

0.05 

0'12 

0'40 

5       .. 

0'22 

0.22 

0-53 

5       ., 

0*92 

o-i6 

0-63 

18       „ 

1-4 

o-o8 

0-31 

60       ,,           ,, 

2-2 

0-24 

0-55 

3       .. 

0-49 

o-i8 

o-3» 

H       ,. 

0-53 

0'20 

0-45 

7       .. 

0-4 

o-i6 

0*27 

30       „ 

1-2 

o-i6 

0-29 

5"8       „          „ 

32-3 

[0-25 

0-38 

Jalap 

Sodium  sulphate   .... 

*  Prevost,  Comptes  rcndus,  1874,  t.  Ixxix.p.  381. 
f  Laffter,  Vcrsuche  zur  Physiologic  der  Gallcnsecretion,  Diss.  Inaug 
1873,  p.  24. 


Breslau, 


Table  of  Cholagogues. 


177 


• 

Dose  in 

Secretion  of 

grains  for  ki- 

bile for  kilo- 

Drug. 

Total  dose  in  grains. 

logramme 

gramme  of 

of  body 

body-weight : 

weight. 

an  hour. 

Before 

After 

c.c. 

C.C. 

Potassium  sulphate       .... 

232 

kvithout  bile 

107 

0-31 

0-47 

Sodium  phosphate 

201 

))           1) 

7-4 

0-27 

0-44 

Rochelle  salt 

463 

with         ,, 

37"o 

0-23 

0-33 

Dilute  nitro-hydrochloric  acid 

36-4 

without  „ 

2-0 

o-ii 

0-39 

Mercuric  chloride 

1 
b 

with        ,, 

0-0077 

0-17 

0-47 

,,               ,,                .         , 

,, 

)i           11 

o'oo7i 

0-20 

0-55 

f  Mercuric  chloride 
(.Calomel 

^0 

I 

"           )' 

0-005  7 
o-ioi  S 

0-48 

0-72 

f  Mercuric  chloride 
\  Calomel 

I 

" 

0-00277 
0-054   ^ 

0-22 

0-85 

Extract  of  physostigma 

2 

!)                     J> 

0-0074 

o-og 

0-36 

))                     ))                   • 

2 

))                      )) 

0-0147 

0-13 

0-75 

Baptisin         .... 

7 

M                     >> 

0-303 

0-23 

0-39 

,, 

7 

!>                     11 

0-374 

0-12 

0-29 

Phytolaccin 

2 
2 

))                     5) 

0-064 
0-104 

0-144 
0-338 

0-29 
0-47 

Hydrastin 

2 

0-077 

0-23 

0-38 

)) 

2 

,,                      „ 

0-147 

o-og 

0-32 

Juglandin 

5 

>l                     11 

0-236 

o-io 

0-28 

10 

,,                      ,, 

0-472 

o-io 

0-32 

Sodium  benzoate  . 

20 

without    ,, 

1-320 

0-22 

0-64 

Ammonium  benzoate    . 

20 

If           1) 

0737 

0-24 

0-54 

Sodium  salicylate 

20 

))              n 

i-ooo 

0-17 

0-56 

))             ))                    •         • 

25 

))               )' 

1-550 

0-26 

0-66 

»             „                    .         . 

20 

,. 

2-150 

0-32 

0-89 

Dr.  Rutherford  does  not  profess  to  be  able  to  explain 
the  exact  manner  in  which  the  cholagogues  that  he 
names  act.  The  gall-bladder  and  the  gall-ducts  may 
be  the  means  by  which  a  more  rapid  expulsion  of  the 
bile  may  be  brought  about ;  and  if  these  be  excited  by 
drugs,  that  might  be  one  way  in  which  cholagogues 
act.  But  it  will  be  said  that  in  Dr.  Rutherford's  ex- 
periments, the  gall-bladder  and  gall-ducts  were  thrown 
out  of  play.  It  may  be  acknowledged  that  the  gall- 
bladder was  excluded  ;  but  I  should  feel  hesitation  in 
accepting  the  same  statement  as  to  the  hepatic  ducts  ; 
indeed  the  diagrams  of  the  action  of  some  of  the 
drugs  look  like  the  result  of  a  sudden  contraction  of 
the  ducts.  But  excluding  the  action  of  the  ducts,  there 
would  remain  three  hypotheses :  (i.)  that  the  chola- 
gogues, the  action  of  which  Dr.  Rutherford  has  investi- 
gated, excite  the  mucous  membrane  of  the  duodenum 
and  thereby  cause  a  greater  secretion  of  bile  from  reflex 

N 


1 78  When  are  Cholagogues  useful  ? 

excitement  of  the  liver.  Something  Hke  this  is  seen  in 
the  action  of  sialagogues,  which  cause  a  great  flow  of 
sahva  by  acting  on  the  buccal  mucous  membrane. 
Against  this  theory  is  the  fact  that  those  drugs  which 
most  actively  excite  the  intestinal  mucous  membrane 
do  not  excite  the  secretion  of  the  liver ;  while  the  most 
active  cholagogues  are  those  which  have  no  influence 
on  the  mucous  membrane  :  (ii.)  that  these  cholagogues 
increase  the  flow  of  blood  through  the  liver  ;  a  theory 
thought  to  be  opposed  to  the  fact  that  an  increased 
flow  of  blood  to  the  intestines  is  not  followed  by  in- 
creased secretion  of  bile.  But  an  excess  of  blood  in 
the  intestines  is  followed,  not  always  by  an  excess  of 
blood,  but  sometimes  by  a  want  of  blood,  in  the  liver : 
or  (iii.)  that  these  cholagogues  have  a  direct  action 
upon  the  cells  or  nerves  of  the  liver,  a  theory  to  which 
Dr.  Rutherford  is  himself  inclined. 

It  has  been  seen  that  the  wish  to  increase  the 
amount  of  bile  excreted  by  the  liver  comes  of  a  most 
venerable  antiquity ;  but  it  may  now  be  asked  :  in 
what  diseases  or  in  what  states  would  good  be  done  to 
a  patient  if  the  amount  of  bile  poured  into  the  duo- 
denum were  increased  ?  It  seems  to  me  that  it  would 
be  judicious  to  put  aside  at  once  all  organic  diseases 
of  the  liver,  such  as  cirrhosis,  amyloid  degeneration, 
and  the  like  ;  for  in  them  the  same  kind  of  evil  would 
follow  the  use  of  a  stimulant  to  the  liver,  as  of  certain 
diuretics  in  Bright's  disease  ;  and  one  of  the  first  rules 
of  medicine,  to  give  diseased  parts  rest,  would  be  broken. 
Then  in  cases  of  jaundice,  it  would  surely  be  undesira- 
ble to  attempt  to  increase  the  secretion  of  bile  ;  for  the 
bile  passages  being  already  over-filled,  harm  would  be 
done  by  pouring  fresh  bile  into  them.  Then  comes  the 
long  list  of  disorders  which  the  public  love  to  think  due 
to  "the  bile,"  and  call  "biliousness,"  the  symptoms  of 
which  are  really  due  to  a  catarrhal   state  of  the   gastro- 


Whe7t  are  Cholagogues  useful?  179 

duodenal  mucous  membrane,  as  will  be  seen  in  the 
chapter  on  bilious  disorders.  Would  an  increased  se- 
cretion of  bile  be  good  in  a  bilious  disorder,  that  is, 
gastro-duodenal  catarrh  ?  I  cannot  appeal  to  experi- 
ence on  this  matter ;  but  if  it  be  safe  to  hazard  a 
conjecture  beforehand,  it  would  seem  improbable  that 
the  pouring  of  a  fluid  like  bile  over  an  inflamed  mucous 
membrane  would  relieve  it ;  and  an  efl"ectual  remedy 
is  already  known  in  a  single  mercurial  purge,  followed 
by  a  gentle  alkaline  course.  Dr.  Rutherford  says  he 
has  found  very  decided  benefit  from  administering  four 
grains  of  iridin  at  bedtime  in  cases  of  "biliousness;" 
the  patients  awaking  in  the  morning  and  finding  the 
headache  and  malaise  gone,  and  the  yellow  tongue 
clean  ;  and  he  also  recommends  that  a  dose  of  Piillna 
water  be  taken  after  the  iridin,  and  that  iridin  be  not 
taken  oftener  than  once  a  week,  as  it  leaves  a  some- 
what depressant  eff"ect  behind  it.  Instead  of  iridin.  Dr. 
•Rutherford  would  seem  rather  inclined  to  favour  euony- 
min  in  two-grain  doses,  and  says  that  he  has  "  been 
much  struck  with  the  success  of  euonymin  in  functional 
hepatic  derangement,  in  several  persons  who  had  tried 
nearly  all  the  commonly  used  cholagogues  with  varying 
and  often  very  limited  success."* 

There  is  one  state  in  which  I  can  well  imagine  that 
an  increase  of  bile  might  be  useful ;  and  that  is  at  the 
end  of  an  attack  of  jaundice  when  the  stools  have  be- 
gun to  shew  some  appearances  of  returning  colour,  but 

*  Rutherford,  British  Medical  yoiirnal,  1879,  vol.  i.  p.  178. 

I  know  that  functional  hepatic  derangement  is  often  talked  about ;  and  I  fear 
that  some  will  think  it  a  disgraceful  confession  when  I  own  my  entire  and  com- 
plete ignorance  of  this  pathological  state.  I  have  never  met  with  it  in  the  post- 
mortem room  and  I  do  not  know  how  it  can  be  recognised  during  life.  Precise 
and  accurate  information  as  to  the  clinical  state,  called  by  some  practitioners  con- 
gestion of  the  liver,  torpor  of  the  liver,  or  sluggish  action  of  the  liver,  is  also 
wanting;  and  also  the  appearances  seen  after  death  in  these  diseases  ;  or  if  they 
do  not  prove  fatal,  the  grounds  on  which  the  symptoms  are  linked  to  a  disturbance 
in  the  functions  of  the  liver. 

N  2 


r8o  Increase  of  Bile  in  Stools. 

the  conjunctiva,  skin,  and  urine  of  the  patient  still 
remain  yellow.  In  this  case  a  stimulus  to  the  secretion 
of  bile  may  possibly  be  of  much  use  ;  and  in  former 
times  the  benzoates  have  been  successfully  used  for  this 
purpose. 

If  the  office  of  the  bile  were  better  known,  it  would 
be  easier  to  say  in  what  states  an  increase  of  this  hu- 
mour may  be  wished  for.  Modern  physiology  seems 
rather  to  be  on  the  way  of  returning  to  the  opinion  of 
Aristotle  that  the  bile  is  an  excrement,  though  not  an 
immediate  excrement,  as  great  part  of  it  is  again  ab- 
sorbed into  the  blood.  The  bile  is  now  thought  to 
have  little  influence  on  the  digestion  of  the  food.  But 
it  may  hereafter  be  proved  to  play  an  important  part  in 
the  metamorphosis  of  the  tissues  ;  and  then  the  amount 
of  bile  secreted  will  enter  into  the  calculations  of  the 
scientific  physician.  Until  Dr.  Rutherford  began  his 
series  of  researches,  the  prescriber  of  drugs  was  alto- 
gether without  trustworthy  knowledge,  whenever  he 
wished  to  increase  the  amount  of  bile  secreted.  There 
was  nothing  to  guide  him  but  the  tradition  of  the 
power  of  calomel.  Now  there  is  a  certain  foundation 
to  build  on,  and  Dr.  Rutherford's  results  and  method 
are  the  beginning  of  a  new  and  reasonable  system  of 
hepatic  therapeutics. 

Though  somewhat  foreign  to  the  subject  of  this 
chapter,  yet  it  may  be  convenient  here  to  consider 
whether  any  drugs  have  the  property  of  causing  un- 
changed bile  to  appear  in  the  stools.  It  will,  I 
suppose,  be  granted  by  the  chemists  that  in  health 
the  unaltered  bile  pigments  cannot  be  found  in  the 
faeces.  Yet  there  can  be  no  doubt  that  the  colour 
of  the  faeces  in  health  is  due  to  the  presence  of  the 
bile,  however  much  the  pigments  may  be  changed ; 
for  if  the  bile  duct  of  an  animal  be  tied,  or  if  in  man 
disease  obstruct  the  duct,  the  faeces   at   once  lose  their 


Colour  of  Stools.  i8i 

natural  colour  and  become  white.  But  between  ac- 
knowledging that  the  colour  of  the  faeces  in  health  is 
due  to  the  bile,  and  that  all  the  variations  in  colour 
seen  in  disease  are  due  to  the  bile,  there  is  a  wide 
distance.  Formerly  a  high  colour  was  thought  evidence 
of  increase  of  bile  in  the  faeces.  Purgatives  often  bring 
away  high-coloured  stools;  therefore  purgatives  increase 
the  amount  of  bile  in  the  faeces. 

This  reasoning  should,  however,  long  have  been 
abandoned.  It  is  well  known  that  many  drugs  given 
by  the  mouth  cause  the  faeces  to  become  black;  for 
example,  charcoal,  iron,  bismuth  ;  and  that  the  pre- 
sence of  blood  gave  a  black  colour  to  the  stools  was 
known  to  Hippocrates. 

The  want  of  colour  in  the  faeces  is  almost  universally 
set  down  to  a  decrease  in  the  secretion  of  bile.  But  I 
should  like  to  point  out  that  of  this  there  is  no  evidence. 
The  absence  of  bile  is,  no  doubt,  the  cause  of  the  white 
stools  in  jaundice  ;  but  it  would  be  highly  imprudent  to 
assert  that  it  is  the  only  cause  of  want  of  colour  in  every 
disease.  In  many  kinds  of  brutes,  the  f^ces  are  grey 
or  even  white  in  health,  and  in  some  of  these,  as  in  the 
dog,  there  is  evidence  that  the  liver  is  as  active  as  in 
man.  The  colour  of  the  fasces,  then,  is  not  due  to  the 
want  of  the  secretion  of  bile  ;  it  is  rather  more  likely  to 
be  due  to  the  absorption  of  the  bile  after  it  have  passed 
into  the  intestine.  Then  on  certain  diet,  as  milk,  the 
stools  often  become  light  coloured  ;  yet  there  is  no  evi- 
dence of  a  decreased  secretion  of  bile,  or  of  an  increased 
absorption  of  bile  from  the  intestine.  It  is  easy  to 
imagine  a  cause  for  this  lack  of  colour,  but  there  is  no 
certain  knowledge  about  it. 

In  judging  of  the  presence  or  absence  of  bile  in  the 
faeces,  chemical  analysis  is,  in  my  opinion,  the  only 
trustworthy  guide. 

It  is  well  known  that  calomel,  in  purgative  doses, 


i82  Bile  in  Stools. 

brings  away  stools  of  apeculiar  green  colour,  compared 
to  that  of  spinach.  Michea  attempted  by  a  chemical 
analysis  to  prove  that  this  colour  is  due  to  the  presence 
of  bile.  He  discarded  Pettenkofer's  test,  as  he  found 
it  troublesome  to  apply  ;  but  availed  himself  of  the  well- 
known  reaction  of  the  bile  pigments  with  nitric  acid. 
He  found  no  play  of  colours  in  the  stools  of  healthy 
men  and  women  ;  but  in  one  case  of  embarras  gastrique 
out  of  three,  the  action  was  distinct  enough  in  the 
vomited  matters  and  green  stools.  Calomel  was  given 
to  eight  persons  suffering  from  constipation :  in  four, 
green  stools  were  passed ;  and  in  two  of  these  four,  nitric 
acid  detected  the  presence  of  bile.  Sulphate  and  phos- 
phate of  soda,  jalap,  and  castor  oil  were  given,  but  the 
stools  had  not  the  green  colour  of  calomel  stools,  nor  did 
nitric  acid  give  the  peculiar  reaction.*  Radziejewski, 
on  the  other  hand,  gave  calomel  to  a  dog  with  a  biliary 
fistula,  in  which,  therefore,  no  bile  could  enter  the  in- 
testine ;  and  saw  the  accustomed  loose  stools  of  a  green 
colour,  but  in  these  no  bile  pigment  could  be  found. 
It  was  further  shown  by  Radziejewski  that  undecom- 
posed  bile  is  but  rarely  found  in  the  faeces  after  the 
action  of  purgatives  of  any  sort ;  out  of  nearly  forty 
experiments  on  dogs,  undecomposed  bile  was  only 
found  four  times,  after  calomel,  castor  oil,  senna,  and 
croton  oil,  and  even  then  the  reaction  was  somewhat 
doubtful. t  The  appearance  of  the  faeces  was  found 
in  no  way  to  correspond  with  the  results  of  the  chemi- 
cal analysis.  They  were  often  green,  and  yet  gave  no 
reaction  with  Gmelin's  test. 

The  cause  of  the  green  colour  of  the  stools  is  not 
well  made  out.  It  may  very  possibly  be  due  to  some 
compound  of  mercury  ;  for  the  statement  that  mercury 
is  not  to  be  found  in  the  fasces  cannot  be  maintained 

*  Michea,  Union  mid.  1848,  t.  ii.  p.  495. 

t  Radziejewski,  Arch,  f.  Anat.  Phys.  u.s.w.  1870,  p.  37. 


Passage  of  Drugs  into  the  Bile.  183 

after  the  observations  of  Saikowski,*  and  of  Mayencon 
and  Bergeret,t  who  found  that  the  fasces  as  well  as  the 
urine  were  the  chief  vehicles  by  which  mercury  leaves 
the  body.  A  green  colour  is  also  seen  after  some  other 
purgatives  besides  mercury  ;  for  example,  in  the  stools 
of  those  who  make  use  of  the  Carlsbad  and  Marienbad 
waters. 

Drugs  which  pass  into  the  bile.  Several  isolated  ob- 
servations were  made  before  1858,  on  the  drugs  which 
are  found  in  the  bile  after  being  introduced  into  the 
ceconomy  ;  but  it  was  Mosler  who  first  carried  out  a 
definite  research  on  this  point.  Biliary  fistula  were 
made  in  dogs  ;  and  in  a  week  or  more,  the  bodies  to  be 
tested  were  either  injected  into  the  veins  or  else  given 
by  the  mouth. 

Albumen  was  the  first  body  to  which  attention  was 
directed.  Mosler  found  that  it  was  not  a  natural  con- 
stituent of  the  bile  of  dogs.  On  injecting  135  C.C.  of 
warm  water  into  the  crural  vein  of  a  dog,  albumen  ap- 
peared in  the  bile  in  from  2  to  4  hours  after  the  injec- 
tion ;  the  albumen  decreased  in  amount  in  6  to  7  hours 
after  ;  in  8  hours,  only  a  trace  was  found  ;  and  in  8  to 
10  hours,  none.  The  urine  showed  albumen  even  half 
an  hour  after  the  injection. 

Mosler  says  nothing  of  the  way  in  which  the  albu- 
men was  looked  for.  It  is  known  that  the  bile  acid 
salts  have  the  property  of  coagulating  albumen. 

Mosler  satisfied  himself  that  no  grape  sugar  was 
present  in  the  bile  of  dogs  in  health,  and  that  a  great 
quantity  must  be  present  in  the  blood  before  it  ap- 
peared in  the  bile.  After  20,  30,  and  40  grammes  (300 
to  600  grains)  had  been  injected  into  the  crural  vein, 
none   could  be  found  in  the  bile  while  there   was  abun- 

*  Saikowski,  Arch.  f.  path.  Anat.  1866,  Bd.  xxxvii.  p.  346. 

f  Mayengon  and  Bergeret,  yoiirnal  de  VAnatoniie  et  de  la  Physiologie,  1873, 
p.  81. 


184  Passage  of  Drugs  into  the  Bile. 

dance  in  the  urine.  When  65  to  80  grammes  (1000  to 
1200  grains)  were  injected,  the  dog  usually  died  or  was 
killed  ;  and  after  death  sugar  was  found  in  the  contents 
of  the  gall-bladder. 

Cane  sugar  appears  in  the  bile,  as  in  the  urine,  more 
readily.  Only  40  grammes  need  to  be  injected  into  the 
veins. 

One  gramme  (15  grains)  of  iodide  of  potassium  given 
by  the  mouth  could  not  be  detected  with  certainty  the 
same  day  in  the  bile.  The  next  day  two  grammes  (30 
grains)  of  iodide  were  given,  and  a  distinct  reaction 
was  found  with  starch  on  the  third  day.  In  another 
experiment,  one  gramme  of  iodide  was  given  at  7  in  the 
morning ;  and  at  3  in  the  afternoon,  the  bile  gave  dis- 
tinct signs  of  the  presence  of  iodine  ;  the  bile  collected 
from  3  o'clock  to  7  next  morning  gave  no  reaction. 

Six  grammes  (about  go  grains)  of  nitre,  given  by  the 
mouth,  did  not  cause  the  bile  to  show  a  reaction  in- 
dicative of  the  presence  of  nitrates. 

For  three  days  a  dog  was  given  twelve  grains  of  sul- 
phate of  copper  every  day,  in  pills  of  two  grains  each 
every  two  hours.  A  trace  of  copper  was  found  in  the 
bile  on  the  first  two  days  ;  on  the  third,  however,  there 
could  be  no  doubt  about  its  presence,  both  in  the  bile 
and  urine.  Mosler  thinks  that  more  copper  is  excreted 
by  the  bile  than  by  the  urine.  Copper,  however,  would 
appear  to  be  a  constant  constituent  of  bile. 

5  and  10  grains  of  calomel  were  given  by  the  mouth 
to  a  dog  ;  but  no  mercury  was  found  in  the  bile  col- 
lected within  24  hours.  A  chemist  might,  however, 
have  something  to  say  as  to  the  method  employed  for 
getting  rid  of  the  organic  matter  of  the  bile  ;  it  is  quite 
possible  that  in  getting  rid  of  the  organic  matter,  the 
mercury  also  disappeared. 

Autenrieth  and  Zeller  found  mercury  in  the  bile  of  a 
dog,  in   no  very  great  amount,  however,  who  had  been 


Passage  of  Drugs  into  the  Bile.  185 

killed  by  rubbing  the  metal  into  the  skin.  The  bile 
was  also  singularly  thick.*  C.  E.  E.  Hoffmann,  in 
his  inaugural  dissertation  at  Wiirzburg  in  1854,  states 
that  he  found  no  mercury  with  the  microscope  in 
the  bile  or  any  other  part  of  the  animal,  after  metallic 
mercury  or  blue  ointment  had  been  given  by  the  mouth 
or  rubbed  in.  Hoffmann's  experiments  were  made  on 
several  animals,  dogs,  rabbits,  and  cats,  and  on  one 
man.f 

Oesterlen  rubbed  blue  ointment  into  the  skin  of  a 
cat  and  also  gave  the  animal  the  ointment  to  eat.  He 
found  mercury,  apparently  in  the  metallic  state,  in  the 
liver,  and  in  still  greater  quantity  in  the  fluid  green 
bile.J 

Mayen9on  and  Bergeret  used  a  very  delicate  test  for 
mercury  in  their  experiments,  and  they  found  it  in  great 
abundance  in  the  livers  of  rabbits  whom  they  had 
poisoned. §  It  seems  probable  that  it  would  also  be 
found  in  the  bile,  if  looked  for  with  equal  care  ;  and  the 
bile  may  be  one  of  the  sources  of  the  mercury  found 
in  the  stools. 

Quinine  was  given  to  a  dog  in  two  following  days  in 
doses  of  two  grains  each,  so  that  in  two  days  the  dog 
had  about  16  grains  given  it,  that  is,  more  than  one 
gramme.  None  of  this  body  could  be  found  in  urine  or 
bile  of  the  following  day.  It  must  be  remembered  how- 
ever that  it  is  very  hard  to  recognise  the  presence  of 
alkaloids  in  organic  fluids. 

For  two   days   10  grains   (-66)   grm.  of  benzoic  acid 

*  Autenrieth  and  Zeller,  Rail's  Archivf.  d.  Phys.  1807  and  1808,  Bd.  viii.p.  255. 
This  increased  thickness  was  also  noted  by  Roche.  [Diet,  de  med.  et  de  chir.  prat. 
Paris,  1830,  t.  iv.  p.  114,  art.  Bile.) 

f  C.  E.  E.  Hoffmann,  Uebev  die  Atifnahme  von  Qiiecksilber  und  dcr  Fctte  in  den 
Kreislanf.  Diss.  Inaug.  Wiirzburg  1854.  Abstract  in  Canstatt's  jfahresbericht  f. 
1855,  Bd.  i.  p.  80. 

:J:  Oesterlen,  Arch.  f.  phys.  Heilhmde,  1843,  Bd.  ii.  p.  536. 

§  MayenQon  and  Bergeret,  Journal  de  VAnat.  et  de  la  Phys.  1873,  annee  ix. 
p.  81.     Mercury  was  found  in  the  greatest  abundance  in  the  liver  and  kidneys. 


1 86  Passage  of  Drugs  into  the  Bile. 

were  given  to  a  dog  every  two  hours.  Altogether  two 
drachms  were  given  (about  4  grammes.)  Hippuric 
acid  was  found  in  the  urine  but  not  in  the  bile. 

Turpentine  was  also  given  to  the  dog  :  but  although 
the  urine  showed  the  characteristic  smell  of  violets,  yet 
the  presence  of. turpentine  could  not  be  determined  in 
the  bile.  The  bile  had  indeed  a  peculiar  resinous  smell, 
but  no  chemical  proofs  could  be  had.*  This  obser- 
vation is  important  in  its  bearing  upon  the  use  of 
Durande's  remedy,  who  proposed  to  dissolve  biliary 
calculi  by  giving  through  the  mouth  a  mixture  of  aether 
and  oil  of  turpentine. 

Iron,  it  is  known,  is  a  constant  constituent  of  the  bile. 
In  a  man  who  had  made  a  pratice  of  swallowing  clasp 
knives,  and  thus  probably  introduced  metallic  iron 
into  his  stomach,  Marcet  found  the  iron  in  the  bile 
increased  in  amount.  In  150  grains  of  this  bile, 
0'5  grain  of  prussian  blue  was  found,  while  in  150 
grains  of  ordinary  bile,  only  0'2  grain  was  found. f 

Lead  was  first  found  by  Heller  in  the  bile  of  a  man 
who  had  died  of  chronic  poisoning  by  lead.  J 

Annuschat  has  made  some  careful  experiments  to  see 
if  this  metal  can  again  be  recognised  in  the  bile  after 
being  given  by  the  mouth.  A  biliary  fistula  was  estab- 
lisil  id  in  fourteen  rabbits,  and  lead  was  given  at  various 
times  before  the  establishment  of  the  fistula.  Lead  was 
found  in  the  bile,  though  in  small  quantity,  in  all  cases 
in  which  the  metal  had  been  given  shortly  before 
the  fistula  was  set  up.  When  the  lead  had  ceased 
to  be  given  three  or  more  days  before  the  fistula  was 
established,  no  lead  could  be  found  in  the  bile,  though 
small  quantities  could  be  found  in  theliver.§ 

*  Friedrich  Mosler,  Arch.  f.  path.  Anal,  1858,  Bd.  xiii.  p.  29. 

f  Marcet,  Med.  Chir.  Trans.  1823,  vol.  xii.  p.  63. 

+  Heller,  Arch.f.  phys.  u.  path.  Chcmic,  1845,  p.  322. 

§  Alb.  Annuschat,  Arch.f.  cxp.  Path.  1877,  ^^-  'V''-  P-  45- 


CHAPTER   IX. 

The  Physiological  Action  of  the  Bile. 

The  bile  of  animals  has  been  used  in  medicine  from 
the  earliest  times.  In  Hippocrates  it  enters  into  the 
composition  of  pills  and  other  remedies  to  be  taken 
by  the  mouth,  as  well  as  of  pessaries,  suppositories, 
and  applications  to  wounds.  In  the  book  of  Tobit, 
it  is  used  as  a  lotion  for  opacities  of  the  cornea,* 
and  Pliny  mentions  with  horror  and  reprobation  that 
Miletus  had  proposed  human  bile  for  the  same  pur- 
pose.t  In  these  days  ox  bile  has  been  given  in 
capsules  in  cases  of  jaundice  ;  and  Rohrig  has  sug- 
gested that  in  high  fever  bile  acids  might  be  given  to 
bring  dovvn  the  prseternatural  heat  of  the  body. J 

The  physiological  action  of  the  bile  can  hardly  be 
said  to  have  been  studied  until  less  than  30  years  ago. 
There  are  indeed  some  old  experiments  by  Deidier  who 
injected  the  bile  of  patients  who  had  died  of  the  great 
plague  at  Marseilles  into  the  veins  of  dogs,  and  found 
that  the  dogs  were  speedily  killed  ;  when  swallowed, 
the  bile  did  no  harm  ;§  and  Magendie  shortly  states 
that  a  gramme  of  bile  rapidly  injected  into  the  crural 
vein  will  kill  an  animal  in  a  few  moments;  but  the  same 

*  It  is  clear  that  the  book  of  Tobit  was  written  after  the  Babylonish  Captivity ; 
but  the  latest  date  given  to  it  by  any  critic  is,  I  am  told,  the  second  century  be- 
fore Christ. 

f  Plinii  Hist.  Nat.  Lib.  xxviii.  cap.  ii.  "  Miletus  oculorum  suffusiones  felle  homi- 
nis  sanari." 

J  Rohrig,  Arch.  d.  Hcilkimde,  1863,  p.  418. 

§  Deidier,  De  bile  peste  emort.  exp.  quoted  by  Bianchi,  Hist.  Hepatica,  Genevas, 
1725,  Pars  iii.  p.  804.  According  to  Haller  {Biblioth.  Anat.  t.  i.  p.  808.)  these 
experiments  have  been  published  several  times ;  in  jfournal  Savans,  1722,  and 
Phil.  Trans,  n.  370,  as  well  as  separately  at  Zurich  and  Montpellier. 


1 88  Results  of  the  Injection 

quantity  injected  slowly,  or  into  the  vena  porta,  is  harm- 
less.* 

Bouisson  injected  some  120  grammes  of  bile  into  the 
stomach  of  a  dog,  and  then  tied  the  gullet.  After 
ineffectual  efforts  at  vomiting,  a  diarrhoea  was  soon  set 
up.  Bouisson  thinks  this  experiment  aids  the  theory 
that  the  bile  is  a  natural  purgative. "f  Everyone,  how- 
ever, who  has  given  drugs  to  dogs,  will  have  noticed 
that  vomiting  and  purging  follow  the  administration  of 
almost  every  kind  of  drug,  whatever  be  its  physiological 
action :  so  that  little  weight  can  be  given  to  this  single 
experiment. 

Goupil  injected  16  grammes  of  bile  into  the  saphena  of 
a  dog.  Shortly  after,  a  general  disturbance  and  languor 
showed  itself,  but  became  less  and  less  intense,  and  the 
animal  recovered  its  health  without  delay.  The  injection 
of  the  same  quantity  of  bile  into  the  portal  vein  was 
followed  by  no  symptoms  whatever. J  Bouisson,  on 
the  other  hand,  injected  six  grammes  of  human  bile, 
taken  from  the  gall  bladder,  into  the  jugular  veins  of 
rabbits  ;  in  three  cases,  a  sort  of  tetanic  stiffness  shortly 
showed  itself,  quickly  followed  by  death.  On  dissection, 
a  distension  of  the  right  heart,  and  thrombosis  of  the 
pulmonary  artery  were  found.  If,  however,  the  bile  were 
filtered  before  injection,  there  was  a  certain  amount 
of  stupor  and  malaise  which  completely  disappeared 
within  half  an  hour.  Bouisson  thought  that  the  action 
of  the  bile  in  the  fatal  cases  was  merely  mechanical, 
owing  to  the  suspension  of  particles  in  the  bile  too  large 
to  pass  the  capillaries  of  the  lungs.  §  Theodor  von  Dusch 
repeated  these  experiments  with  filtered  bile  and  found 
that  two  rabbits  were  rapidly  killed  with  tetanus  and 

*  Magendie,  Precis  clcmcntairc  de  Physiologic,  Paris,  1836,  46  ed.  t.  ii.  p.  259. 
f  Bouisson,  Dc  la  bile,  Montpellier,  1843,  p.  56. 

X  Goupil,  Essai  sur  la  physiol.  du/oie,  ThiiSQ  de  M.   Renaud,   Strasbourg,  1838, 
quoted  by  Bouisson,  op.  cit.  p.  59. 
§  Bouisson,  op.  cit.  p.  60. 


of  Bile  into  the  Veins.  i8g 

opisthotonos  whether  the  bile  were  injected  into  the  crural 
or  the  jugular  vein  ;  while  the  injection  of  filtered  bile  into 
the  vena  saphena  of  a  dog  was  followed  only  by  a  few 
irregular  contractions  of  the  muscles,  and  by  vomiting ; 
and  in  two  days  the  dog  had  recovered  his  health,* 

There  can  be  little  doubt  that  some  of  these  cases 
of  severe  symptoms  following  the  injection  of  unfiltered 
bile  are  due  solely  to  the  mechanical  impaction  of  solid 
particles  in  the  pulmonary  artery.  If,  however,  the  bile 
have  been  filtered,  the  cause  of  death  is  probably  the 
same,  thrombosis  of  the  pulmonary  artery ;  but  the 
thrombosis  is  due  to  the  solution  of  the  corpuscles  by 
the  bile  acids  and  consequent  formation  of  a  clot."]* 

Johannes  Ranke  and  Sydney  found  no  symptoms 
follow  the  injection  into  the  jugular  vein  of  a  rabbit  of 
the  bile  secreted  by  its  own  liver.J  The  absence  of  all 
appearances  is  probably  due  to  the  small  amount  of 
solids  in  the  bile  freshly  secreted  by  the  liver  of  vege- 
table eaters  ;  and  not  that  the  bile  secreted  by  the 
animal  itself  has  no  influence  over  its  own  oeconomy,  as 
these  writers  believe. 

It  will  be  convenient  in  further  dealing  with  the 
physiological  action  of  the  bile  to  consider  the  experi- 
ments in  sections  corresponding  with  the  chemical 
constitution  of  this  humour  ;  the  bile  acids,  bile  pigments, 
and  cholestearin.  The  bile  acids  show  the  most  active 
physiological  properties,  and  may  therefore  be  consi- 
dered first  of  all. 

Physiological  Action  of   the   Bile   Acids. 

It  has  been  explained,  in  speaking  of  the  chemistry  of 
the  bile,  that  Platner's  crystallized  bile  is  a  mixture  of 

*  Th.  von  Dusch,  Untevsuchungen  und  Experimente  ah  Beitrag  zur  Pathogcncse 
des  Icterus,  u.s.w.     Leipzig,  1854,  p.  17. 

f  See  below,  Action  of  the  Bile  Acids  on  the  Nervous  System. 

X  Johannes  Ranke,  Die  Bliitvcrtheilung  und  der  Thdfigkcitswcchscl  dcr  Organc, 
Leipzig,  1871,  p.  173. 


I  go  Physiological  Action  of  the  Bile  Acids. 

the  soda  salts  of  two  acids,  taurocholic  and  glycocholic 
acid.  These  two  acids  differ  but  Httle  in  their  physio- 
logical action,  taurocholic  acid  being  somewhat  more 
active  than  glycocholic.  Feltz  and  Ritter  found  that 
•46  grm.  of  taurocholate  of  soda  for  each  kilogramme 
of  animal  would  cause  death,  apparently  when  injected 
into  the  blood  vessels  ;  of  the  glycocholate,  '64  grm.  was 
needed  for  each  kilogramme ;  while  of  the  mixture 
of  the  two  salts  (Platner's  crystallized  bile)  "51  grm.* 
Leyden  found  that  less  than  a  gramme  of  bile  acid 
salts  injected  suddenly  into  the  heart  would  at  once 
cause  death  in  a  dog.  An  injection  of  3  or  4  grains 
into  the  carotid  killed  a  dog  in  a  few  minutes.  With 
injections  into  the  blood  done  slowly,  larger  doses, 
nearly  2  grammes,  were  needed  to  kill  dogs  even  in  one 
or  two  days-t 

Johannes  Ranke  has  stated  that  15  milligrammes  are 
enough  to  kill  rabbits  when  injected  into  the  jugular  vein. 
In  this  mode  of  death,  the  bile  acid  salts  kill,  not  by  a 
specific  action  on  the  heart,  but  by  causing  a  throm- 
bosis of  the  pulmonary  artery. J  I  cannot,  from  my 
own  observations,  confirm  Johannes  Ranke's  statement, 
as  I  have  found  rabbits  bear  much  larger  doses  with 
impunity. 

In  these  acids,  the  active  body  would  seem  to  be  the 
cholalic  acid  ;  it  acts  upon  the  heart  and  dissolves  the 
red  corpuscles  with  energy,  while  glycocoll  and  taurin 
have  been  found  to  be  almost  inert. 

Organisms,  apparently  fungi,  were  seen  in  solutions  of 


*  Feltz  and  Ritter,  youriial  dc  V Anatomic  ct  dc  la  Physiologic,  1874,  t.  x.  p.  583. 
These  writers  do  not  expressly  say  whether  the  doses  were  injected  under  the 
skin  or  into  the  blood  ;  apparently  into  the  blood.  Still  less  do  they  say  into 
what  vessel,  whether  the  jugular  or  crural  vein  ;  and  yet  this  is  a  matter  of  some 
importance. 

f  Leyden,  BeHrdge  zur  Pathologic  dcs  Icterus,  Berlin,  1866,  p.  gg. 

X  Johannes  Ranke,  Die  Bliitvcrthcilung  mid  Thdtigkcitswccliscl  dcr  Organc, 
Leipzig,  1871,  p.  164. 


Physiological  Action  of  the  Bile  Acids.  igi 

the  bile  acids  in  water  after  the  solution  had  been  kept 
for  some  weeks.     But  their  growth  is  not  rapid.* 

General  Experiments :  on  the  frog.  If  one  cubic 
centimetre  of  a  lo  or  12  per  cent,  solution  of  Platner's 
crystallised  bile  be  injected  under  the  skin  of  a  frog, 
he  at  once  begins  to  jump  about  as  if  much  excited.  In 
about  five  minutes,  however,  the  movements  become 
less  active  and  in  ten  to  twenty  minutes  the  frog  is 
motionless,  unless  he  be  touched  or  made  to  move. 
The  next  appearance  is  that  the  hind  limbs  begin  to 
abide  where  set  by  the  observer  ;  and  with  great  trouble 
he  draws  the  legs  up  when  they  are  extended  by 
observer.  He  no  longer  springs  but  crawls  :  and  if  put 
on  his  back  cannot  recover  himself.  He  shows  no 
movements  but  those  of  respiration.  In  a  couple  of 
hours  or  so  he  is  commonly  found  lying  relaxed,  no 
longer  in  the  sitting  posture,  with  pupils  contracted, 
and  showing  very  little  or  no  reflex  action. f 

These  phaenomena  may  appear  sooner  or  later.  The 
frog  may  die  in  a  few  hours ;  or  last  on  until  the  third  day. 

In  the  advanced  stage  of  the  action  of  the  bile  acids 
upon  frogs,  I  have  found  that  electrical  irritation  of  the 
nerves  or  muscles  was  commonly  followed  by  lively  con- 
tractions ;  in  some  instances,  however,  I  have  seen  no 
movement  follow. 

I  have  also  repeated  with  the  same  results  an  experi- 
ment first  made  by  Leyden.  A  frog  was  put  into  a 
vessel  holding  enough  of  a  1.  per' cent,  solution  of  bile 
acids  to  cover  the  bottom.  The  frog  was  always  found 
dead  the  next  morning,  and  on  examination  with  the 
microscope  parenchymatous  changes  were  found  in  the 
heart  and  liver. 


*  See  p.  145  on  the  arrest  of  putrefaction  by  the  bile  acids. 

f  In  these  I  give  a  summary  of  my  own  experiments.  It  would  be  tedious  to 
give  the  details  of  each.  See  also  Leyden.  {Beitrdge  ziir  Pathologic  des  Icterus, 
Berlin,  1866,  p.  57.) 


1 92  Physiological  Action  of  the  Bile  Acids. 

Injections  under  the  skin  of  the  rabbit.  Leyden  found 
that  rabbits  died  without  fail  in  2  or  3  days  after  the 
injection  of  6  C.C.  of  a  10  per  cent,  solution  under 
the  skin.  Immediately  after  the  injection  there  was 
excitement,  just  as  with  frogs,  which  also  soon  dis- 
appeared. On  the  first  day,  the  rabbits  took  their 
food  ;  on  the  second,  not  ;  and  they  became  listless. 
Death  -sometimes  took  place  in  the  midst  of  convulsions. 
Bile  acids  were  found  in  the  urine  by  using  Hoppe's 
method,  but  not  bile  pigment.* 

Injection  into  the  Stomach.  Both  Rohrigf  and  LeydenJ 
have  injected  as  much  as  one  or  two  grammes  of  the 
soda  salts  of  the  bile  acids  into  the  stomach  of  rabbits. 
Rohrig  noted  no  symptoms,  while  Leyden  observed  a 
diarrhoea  to  be  set  up,  which  apparently  killed  the 
animal  on  the  7th  day  after  the  injection.  No  bile 
acids  or  bile  pigments  were  found  in  the  urine.  No 
morbid  appearances  were  found  after  death. 

Injection  into  the  bowels.  Rohrig  noted  that  a  slow  pulse 
or  death  invariably  took  place  after  the  injection  of 
cholalate  of  soda,  and  he  thinks  that  the  bile  acids  act 
as  rapidly  after  injection  into  the  rectum  as  into  the 
blood  vessels. §  This  is  a  matter  of  some  interest  in 
in  the  physiology  of  the  bile. 

Leyden  injected  several  C.C.  of  10  per  cent,  solution 
of  bile  acids  into  the  rectum  of  two  rabbits.  Diarrhoea 
came  on  in  both  cases,  and  in  one  opisthotonos.  Bile 
acids  were  recognised  in  the  urine  of  both.  || 

A  curious  symptom  was  noted  by  von  Dusch,^ 
Kiihne,^*  and  Feltz  and  Ritter,tt  and  others  during  the 

•  Leyden,  op.  cit.  p.  66. 

f  Rohrig,  Arch.  d.  Hcilkundc,  1863,  p.  414. 

X  Leyden,  op.  cit.  p.  68.  §  Rohrig,  loc.  cit.  ||  Leyden,  op.  cit.  p.  67. 

51  Th.  von  Dusch,  Uiitcrsuchungcn  nnd  Expcrimcnte  ah  Beitrdg  zur  Patliogcnesc 
des  Icterus,  Leipzig,  1854,  p.  20. 

•♦  Kiihne,  Arch.f.  path.  Anat.  1858,  Bd.  xiv.  p.  324. 

ff  Feltz  and  Ritter,  yournal  dc  V Anatomic  et  de  la  Physiologic,  1874,  t.  x.  p.  576 
et  scqq. 


On  the  Red  Blood  Corpuscles.  193 

injection  of  the  acids  into  the  vein  ;  the  creature  thrusts 
out  its  tongue  and  licks  its  Hps  as  if  to  free  itself 
from  some  disagreeable  taste.  I  have  noted  this  appear- 
ance myself  repeatedly.  It  is  possible  it  may  be  due  to 
the  presence  of  the  bitter  bile  acid  salts  in  the  blood. 

Feltz  and  Ritter  have  also  remarked  an  exaggeration 
of  all  the  secretions,  ptyalism,  increased  secretion  of 
the  mucus  of  the  nose,  abundance  of  urine,  and  loose 
stools.  They  look  upon  these  symptoms  as  an  effort 
of  the  oeconomy  to  eject  the  poison.  This  is  quite 
a  possible  explanation  ;  but  salivation  and  purging  are 
so  often  seen  in  dogs  after  any  drug  that  they  can 
hardly  be  regarded  as  peculiarities  of  the  action  of  the 
bile  acids.  Mr.  Graham  Brown  noticed  no  salivation 
nor  vomiting,  and  no  diarrhoea,  unless  the  dose  were 
large,  in  rabbits  under  whose  skin  the  bile  acid  salts  had 
been  injected.* 

On  the  Red  Blood  Corpuscles.  It  is  commonly  said  by 
the  Germans  that  Hiinefeld  was  the  first  to  note  that 
bile  dissolved  the  corpuscles. f  I  have  found,  however, 
that  this  appearance  was  seen  much  earlier.  Senac 
noticed  that  pus  and  bile,  mixed  with  blood,  lessened 
the  red  part  of  the  blood.J  Portal  plainly  asserts  that 
in  experiments  of  his  own  he  had  seen  that  the  bile 
mixed  with  blood  dissolved  the  red  globules. § 

Hiinefeld  found  that  the  blood,  as  soon  as  mixed 
with  bile,  became  clear,  and  that  the  blood-corpuscles 
disappeared  in  a  moment.  The  bile  of  man,  oxen, 
dogs,  pigs,  cats,  rabbits,  hens,  toads,  frogs,  and  fish,  had 
the  same  action  upon  the  blood  of  men,  pigs,  and  frogs  ; 


*  Graham  Bzo^nxi,  Proceedings  of  the  Royal  Society  of  Edinbuygh,  1875,  Vol.  viii. 

P-527- 

f  Hiinefeld, D^r  Chemismus  inder  thicrischen  Organisation,  Leipzig,  1840,  p.  49. 

X  Senac,  quoted  by  Portal,  Obs.  sur  la  nature  et  le  traitenicnt  des  nial.   du  foie, 
Paris,  1813,  p.  156. 

§  Portal,  op.  cit.  p.  134,  note.      He  quotes  from  his  Mcnioircs,  t.  ii.  p.  279,  but  I 
have  not  been  able  to  verify  this  reference. 

O 


194  Action  of  the  Bile  Acids 

only  the  nuclei  of  the  frog's  blood  corpuscles  remained 
for  a  time  unchanged,  and  then  broke  up  into  granules 
which  at  last  disappeared.  The  bile  of  a  still-born 
infant,  which  was  free  from  bitterness,  had  none  of  this 
property.  That  of  a  man  who  died  of  a  diabetes,  very 
little. 

On  the  other  hand,  Henle  says  that  ox-bile  is  the 
best  thing  in  the  world  in  which  to  keep  the  red 
corpuscles  of  frogs ;  and  remarks  that  Hiinefeld. 
has  not  taken  note  of  the  concentration  of  the  bile.* 
Frerichs,  too,  says  that  the  contents  of  the  gall-bladder 
dissolve  the  red  corpuscles  less  readily  than  does  dis- 
tilled water.f  He  is  inclined,  however,  to  admit  that 
the  salts  of  the  bile  acids  may  possess  the  property  of 
.  dissolving  the  red  corpuscles. 

But  most  observers  support  the  original  statements 
of  Hiinefeld.  The  latest  experiments  on  this  matter, 
those  of  Koloman  Miiller,  confirm  them.  Equal  parts 
of  filtered  bile  and  blood  were  mixed,  and  though  the 
decrease  of  the  red  corpuscles  could  not  in  all  cases 
be  at  once  detected,  yet  after  a  certain  time,  say  an 
hour,  it  could  always  be  noted,  and  in  the  end  not  a 
single  corpuscle  could  be  found.  J 

After  the  discovery  of  the  composition  of  the  bile 
acids  by  Strecker,  Theodor  von  Dusch  was,  as  far  as  I 
can  make  out,  the  first  to  show  that  the  solvent  power 
of  the  bile  upon  the  red  corpuscles  was  due  to  the  pre- 
sence of  the  bile  acids  in  this  humour.  Two  or  three 
crystals  of  glycocholate  of  soda  were  placed  in  a  watch- 
glass  with  a  drop  of  human  blood ;  after  a  few  minutes 
a  transparent  bright-red  circle  was  found  around  the 
the  crystal,  which  in  lo  minutes  had  extended  all  over 
the   fluid  ;    under  the  microscope,   no  trace   of  the   red 

*  Henle,  Allg.  Atiat.  Leipzig,  1841,  p.  430. 

t  Frerichs,  KUnik  d.  Lebcykranhheitcn,  Braunschweig,  1858,  Bd.  i.  p.  100. 

X  Koloman  Miiller,  Arch.f.  exp.Path.  1873,  Bd.  i.  p.  222, 


•  upon  the  Red  Blood  Corpuscles.  195 

corpuscles  could  be  found.  Taurocholate  of  soda 
showed  the  same  property,  but  in  a  higher  degree. 
With  taurin  itself,  the  blood-corpuscles  were  not  dis- 
solved, and  this  experiment  has  been  confirmed  by 
Koloman  Miiller.*  Cholalate  of  soda  gave  the  same 
appearances  as  glycocholate  of  soda.f 

Kiihne  went  a  step  farther,  and  examined  the  blood- 
corpuscles  under  the  microscope  at  the  moment  that 
they  were  acted  upon  by  the  solution  of  the  bile  acids. 
He  allowed  the  blood  and  the  solution  to  run  together 
under  the  covering  glass.  If  a  single  red  blood-cor- 
puscle were  kept  under  the  microscope,  it  disappeared 
completely,  without  first  losing  its  cupped  shape,  or 
increasing  in  size,  or  losing  its  definition. J  I  can  fully 
support  this  statement  of  Kiihne's  as  to  the  sudden  and 
complete  extinction  of  the  red  corpuscle  when  it  touches 
the  bile  acid  solution.  I  can  only  describe  the  appear- 
ance by  saying  that  at  one  moment  the  red  corpuscle 
.is  seen,  and  that,  at  the  next,  it  is  no  longer  there. 
It  disappears  without  suffering  any  change  in  shape 
or  colour.  Traube  compares  it  to  the  melting  of 
snow  in  warm  water  ;§  a  comparison  which  I  do  not 
think  good,  as  snow  does  not  melt  so  rapidly  as  the 
corpuscle.  The  way  in  which  distilled  water  or  strong 
salt  solution  acts  is  so  different  that  the  destruction  of 
the  red  corpuscle  cannot  be  set  down  to  the  changes  in 
the  specific  gravity  of  the  fluid.  In  my  own  experi- 
ments I  used  a  solution  of  bile  acids  12  per  cent,  that  is 
twice  the  strength  of  that  of  Kiihne. 

Kiihne  confirms  the  statement  of  von  Dusch,  that  the 
salts  of  cholalic  acid  have  the  same  action  on  the  red 
corpuscles,  and  Kiihne  also  finds  that  the  same  is  true 
of  choloidic  acid. 

*  Koloman  Miiller,  op.  cit.  p.  224. 

f  Th.  von  Dusch,  op.  cit.  pp.  13  et  seqq. 

X  Kiihne,  Arch.  f.  path.  Anat.  1858,  Bd.  xiv.  p.  333. 

§  Traube,  Berlin,  klin.  Wochenschrift,  1864,  p.  86. 

O  2 


196  Action  of  the  Bile  Acids 

The  destruction  of  the  red  corpuscle  is  complete,  and 
no  membrane  can  be  brought  again  into  view  by  the 
action  of  iodine,  or  other  colouring  matter.  But  Kuehne 
finds  that  this  is  only  true  of  the  red  corpuscles  of 
mammals  and  birds.  Though  the  bile  of  all  vertebrates 
can  dissolve  the  mammalian  red  corpuscle,  yet  the  bile 
acids  do  not  act  upon  the  red  corpuscle  of  frogs  as  they 
act  upon  that  of  mammals.*  The  disappearance  is 
slower,  the  corpuscle  changes  its  shape,  but  at  last  the 
whole  of  it  becomes  invisible.  If,  however,  water  be 
added,  or  better,  solution  of  iodine,  it  becomes  evident 
that  the  membrane  of  the  corpuscle  has  not  been  dis- 
solved for  it  is  brought  into  view  again. 

On  Leucocytes.  Th.  von  Dusch  declares  that  leu- 
cocytes are  dissolved  by  bile,t  a  statement  agreed  to 
by  Charcot.  J  An  increase  of  the  white  corpuscles  in 
the  blood  of  animals  poisoned  by  the  bile  acids  was 
noted  by  Leyden§  and  Mr.  Graham  Brown.  || 

On  the  Gases  of  the  Blood.  Feltz  and  Ritter  found  a 
slight  decrease  in  the  amount  of  oxygen  contained  in 
the  blood  of  a  dog  poisoned  by  the  bile  acid  salts,  to- 
gether with  a  slight  increase  in  the  amount  of  carbonic 
acid  and  nitrogen  ;  and  they  found  that  blood  which 
contained  one  and  two  per  cent,  of  glycocholate  of  soda 
took  up  less  oxygen  and  held  more  carbonic  acid  than 
blood  which  was  free  from  glycocholates.^l  The  in- 
crease and  decrease  are,  however,  so  small  that  they 
seem  to  me  quite  within  the  bounds  of  errors  ol  estima- 
tion. 


*  F.  Simon  {Animal  Chcmhtry,  Day's  translation,  London,  1845,  vol.  i.  p.  106.) 
had  noticed  that  the  corpuscles  of  the  frog  were  not  very  soluble  in  bile. 

f  Th.  von  Dusch,  op.  cit.  p.  15. 

X  Charcot,  LcQons  siir  les  maladies  dufoic,  Paris,  1877,  p.  75. 

§  Leyden,  op.  cit.  p.  67. 

II  J.  Graham   Brown,  Proceedings  of  the  Royal  Society  of  Edinburgh,    1875, 
Vol.  viii.  p.  520. 
■  %  Feltz  and  Ritter,  Jotirnal  de  V Anatomic  ct  dc  la  Physiologic,  1874,  t,  x.  p.  587. 


upon  the  Liver  Cells.  197 

On  the  Liver  Cells.  Th.  von  Dusch  first  paid  atten- 
tion to  the  action  of  bile  upon  the  Hver  cells.  He  came 
to  the  conclusion  that  bile,  especially  if  concentrated, 
made  the  liver  cells  transparent  and  pale,  and  at  last 
reduced  them  to  a  finely  granular  detritus.*  But 
Kiihne  has  shown  that  this  solution  of  the  cells  is 
only  apparent.  Under  the  microscope  it  is  true  that 
the  outline  of  the  cell  is  lost,  while  apparently  the  con- 
tents are  set  free.  But  the  contents  do  not  separate 
from  one  another ;  and  if  the  preparation  be  washed 
with  water,  the  outline  of  the  cells  returns.  In  my  own 
observations  made  in  1873,  with  the  livers  of  freshly 
killed,  healthy  mammals,  the  bile  taken  from  the  gall 
bladder  was  added  to  the  cells  floating  in  saline  solu- 
tion, and  the  same  appearances  as  those  described  by 
Kiihne  were  seen.  The  cells  lost  their  shape ;  they 
became  rhomboidal,  pale,  and  it  was  hard  to  make  out 
the  nucleus.  The  outline  of  the  cell  became  altogether 
indistinct.  Thus  far  the  experiment  seemed  in  favour 
of  von  Dusch's  views.  But  the  contents  of  the  cells 
never  became  free.  If  made  to  move,  they  floated  away 
and  preserved  the  same  relation  to  one  another.  Further, 
if  acted  on  by  iodine,  the  outline  of  the  cell  again  came 
into  view.  Like  changes  in  the  cells  were  seen  with  a 
12  per  cent,  solution  of  the  bile  acids. 

Robin  is  also  of  opinion  that  the  bile  does  not  dis- 
solve the  liver  cells. f 

On  the  other  hand,  Kiihne  believes  that  this  only 
holds  good  of  the  liver  cells  of  mammals  and  birds.  In 
the  livers  of  frogs,  taken  in  the  spring,  it  could  be  seen 
that  the  outline  became  pale  ;  and  then,  that  the  con- 
tents of  the  cell,  which  were  made  up  of  pigment  and 
fine  colourless  granules,  suddenly  burst  out,  and  fol- 
lowed the  course  of  the  stream.     It  is  thus  a  very  curious 

*  Th.  von  Dusch,  op.  cit.  p.  36. 

I  Robin,  Lcgons  sur  les  huincnrs,  Paris,  1867,  p.  530. 


igS  Action  of  the  Bile  Acids 

and  noteworthy  fact  that  the  cells  of  the  liver  of  the 
frog  should  dissolve  in  bile,  while  the  red  corpuscles 
resist.* 

On  the  glands  and  muscles.  Like  many  other  poisons, 
the  bile  acids  cause  a  parenchymatous  degeneration  of 
the  glands  and  muscles.  Leydenf  found  this  result  in 
very  many  of  the  frogs,  under  whose  skin  i.  C.C.  of  a 
lo  per  cent,  solution  of  the  bile  acids  had  been  injected. 
But  it  was  not  seen  in  all.  I  can  testify  to  the  accuracy 
of  Leyden's  observations  on  frogs,  but  I  have  not  been 
able  to  see  the  same  appearance  in  rabbits,  probably 
owing  to  the  short  time  that  the  poison  was  allowed  to 
act,  as  Leyden  found  changes  in  two  rabbits  on  whom 
the  bile  acids  had  been  allowed  to  act  at  least  twelve 
hours,  but  not  in  a  third.  Parenchymatous  changes 
were  also  seen  in  dogs.  Feltz  and  Ritter,  too,  found 
like  changes  in  the  liver  and  kidneys  of  dogs, J  Mr. 
Graham  Brown  in  those  of  rabbits, §  and  Kemarsky  in 
both  of  these  animals.  || 

On  striped  muscles.  As  early  as  1852,  Budge  made 
some  experiments  on  this  matter,  and  found  that  if 
/rog's  bile  be  laid  upon  the  muscles  of  the  frog's  thigh, 
there  followed  a  rapid  contraction  of  the  muscle ;  if  the 
muscle  had  been  cut  into  beforehand,  there  was  a  very 
marked  contraction  as  a  consequence  of  the  irritation.^ 
Kiihne  also  stated  that  bile  acted  as  a  marked  excitant 
of  muscles,  whether  applied  to  the  nerves  or  direct  to 
the  muscles  ;  and  that  the  difference  of  observations 
was  due  to  the  varying  degrees  of  concentration  in  the 
bile  itself.** 

•  Kiihne,  op.  cit.  p.  335. 

•j-  Leyden,  Bcitrdgc  zur  Pathologic  des  Icterus,  Berlin,  1866,  p.  60. 
J  Feltz  and  Ritter,  yournal  de  V Anatomic  ct  dc  la  Physiologic,  1874,  t.  x.  p.  575. 
§  J.  Graham   Browne,   Proceedings  of  the  Royal  Society   of  Edinburgh,  iSjS, 
Vol.  viii.  p.  531. 

II  Kemarsky,  Hofmann  and  Schwalbe's  Jahrcsbcrichtc  f.  1875,  p.  172. 
IT  Budge,  Froriep's  Tagesbcr.  1852,  No.  475,  p.  343. 
**  Kiihne,  Arch,  f,  Atiat.  Phys.  u.s.w.  1859,  p.  235. 


tipon  Voluntary  Muscles.  igg 

Leyden  found  that,  If  the  muscle  of  a  frog  be  touched 
with  a  solution  of  bile  acids,  small  fibrillary  contrac- 
tions are  seen.  If  a  vStrong  solution  be  used,  the  spot 
touched  becomes  whitish  and  opaque,  and  the  whole 
muscle  somewhat  contracted.* 

The  observations  of  Albersf  on  the  muscles  and 
nerves  may  be  here  passed  by,  as  they  are  general  ex- 
periments and  prove  nothing  directly  as  to  the  muscles. 

Johannes  Ranke  injected  a  i  per  cent,  or  a  '5  per  cent. 
of  solution  of  glycocholate  of  soda  into  the  hind  limbs 
of  frogs,  and  found  that  the  muscles  became  as  hard 
as  wood,  and  no  longer  gave  tracings  when  acted-  on 
by  electricity.  On  passing  saline  solution  through  the 
vessels  of  the  limb,  the  muscles  became  much  swollen 
and  transparent.  He  concludes  that  the  bile  acids  have 
a  direct  paralysing  action  on  muscles  ;  not  a  weaken- 
ing action  like  carbonic  acid.  The  swelling  of  the 
muscle  after  the  injection  of  the  saline  solution,  and 
failure  of  the  washing  out  of  the  muscle  to  restore  its 
function  show  that  the  muscle  is  changed  in  its  chemi- 
cal composition. J 

In  this  last  sentence  I  quite  agree  with  Ranke,  and 
I  believe  that  all  the  phsenomena  described  by  him  and 
by  Budge  and  Leyden  may  be  explained  on  chemical 
grounds.  In  repeating  Ranke's  experiments,  I  noticed 
all  the  phsenomena  which  he  has  described.  There 
were  the  irregular  contractions  of  the  muscles  of  the 
limbs  as  the  injection  passed  into  them,  rigidity  and 
hardness  immediately  after  the  injection,  and  an  ab- 
sence of  contraction  on  the  application  of  electricity  to 

*  Leyden,  op.  cit.  p.  97. 

f  J.  F.  H.  Albers,  Arch.  f.  path.  Anat.  1862,  Bd.  xxiii.  p.  582. 

X  Johannes  Ranke,  ^rc/i. /.  Anat.  Phys.  u.s.w.  1864,  p.  340;  also  Tetanus, 
Leipzig,  1865,  P-  395'  After  injecting  bile  acids  into  the  femoral  artery  of  a  dog 
towards  the  periphery,  Leyden  found  the  corresponding  muscles  stiff  and  hard  to 
the  touch,  while  the  animal  could  not  use  the  limb.  After  death  on  the  third 
day,  the  muscular  fibres  showed  a  well-marked  granular  change.  [Bcitrdgc  zur 
Pathologie  des  Icterus,  Berlin,  1866,  p.  82). 


200  Action  of  the  Bile  Acids 

the  sciatic  nerves.  Knowing,  however,  that  bile  acids 
will  coagulate  albumen,  as  a  i  per  cent,  solution  will 
cause  turbidity  in  white  of  &gg,  it  would  seem  that  the 
appearances  described  by  Ranke  would  be  very  fully 
explained  by  the  chemical  action  of  the  bile  acids  upon 
the  albuminous  bodies  of  the  muscle. 

I  was  thus  led  to  make  a  series  of  experiments  in 
which  the  bile  acids  should  not  be  immediately  injected 
into  the  muscle,  but  should  act  by  the  natural  process 
of  absorption.  The  solution  of  the  bile  acids  was  in- 
jected into  the  lymphatic  sac,  or  under  the  skin  of  frogs. 
The  amount  given  varied  from  '05  to  "3  grm.  Twelve 
experiments  were  made  ;  and  in  nearly  all  no  change 
in  the  curve  traced  by  the  myograph  could  be  detected 
after  the  injection  of  the  bile  acids,  the  observations 
beginning  immediately  after  the  injection  of  the  bile 
acids,  and  lasting  up  to  the  time  that  the  muscles  would 
respond  to  any  amount  of  electricity  that  I  was  able  to 
bring  to  bear  upon  them. 

The  method  used  was  as  follows  :  the  sciatic  nerve 
was  prepared,  carefully  avoiding  all  injury  of  blood- 
vessels ;  the  tendon  of  the  gastrocnemius  was  attached 
to  a  string,  and  separated  from  the  heel.  The  frog  was 
then  put  into  a  moist  chamber,  and  the  string  attached 
to  the  tendo  A  chillis  fastened  to  a  telegraph  lever  writing 
on  a  revolving  cylinder.  The  sciatic  nerve  was  then  irri- 
tated by  means  of  electricity  from  a  Du  Bois-Reymond's 
coil ;  it  was  applied  not  oftener  than  once  every  minute, 
and  only  of  such  amount  as  to  cause  the  muscle  to  con- 
tract. In  the  first  two  or  three  experiments  the  injec- 
tion was  given  before  the  muscle  was  ready. 

As  samples  of  the  others  I  detail  two  of  these  experi- 
ments. 

Jan.  22nd.  Excellent  normal  curves  obtained,  "i  grm. 
of  bile  acids  injected  under  skin  of  back.     No  change  in 


upon  the  Heart.  201 

the  curves  save  that  they  grow  smaller  in  height  from 
15  to  60  minutes  after  injection. 

Feb.  2nd.  "3  grm.  of  bile  acids  injected  under  skin 
of  back.  No  change  in  the  normal  curves  from  ig  to  92 
minutes  after  injection. 

Upon  the  heart.  It  has  long  been  known  that  in  some 
cases  of  jaundice  the  pulse  becomes  slow.  But  Rohrig 
deserves  the  credit  of  having  been  the  first  to  point  out 
that  it  was  the  action  of  the  bile  acids  which  caused  the 
slow  pulse  ;  and  that  it  was  not  the  bile  pigments  or 
cholestearin. 

He  found  that  if  a  quantity  not  less  than  2  C.C.  of 
filtered  ox  bile  were  injected  into  the  jugular  vein  of 
rabbits,  a  distinct  decrease  in  the  number  of  the  heart 
beats,  7  or  8  in  the  15  seconds,  could  be  made  out  with 
the  stethoscope.  An  injection  of  6  C.C.  of  bile  would 
bring  down  the  pulse  of  rabbits  to  27  or  30  beats :  and 
by  repeated  doses,  only  12  or  13  beats  would  be  heard 
in  two  minutes,  and  death  take  place,  due  as  Rohrig 
states  to  paralysis  of  the  heart. 

Rohrig  found  that  the  pigments  and  the  cholestearin 
had  no  action  on  the  pulse ;  neither  had  taurin  nor  glyco- 
coll ;  the  soda  salts  of  glycocholic  and  taurocholic  acid, 
on  the  other  hand,  had  the  same  action  as  the  bile  had 
itself,  and  the  soda  salts  of  cholalic  acid  were  still  more 
active.  It  is  thus  seen  that  the  active  elements  in  the 
bile  are  the  conjugate  acids  ;  and  that  it  is  the  cholalic 
acid,  not  the  basic  glycocoU,  nor  the  taurin,  that  is  the 
agent  of  the  slow  pulse. 

Rohrig  further  found  that  the  slow  pulse  appeared 
when  the  vagi  had  been  cut,  and  also  that  the  frog's 
heart,  when  cut  out  and  plunged  in  a  solution  of  bile 
acids,  beat  a  fewer  number  of  times  than  when  cut  out 
and  plunged  in  serum,  or  distilled  water  ;  and  from 
these   data  he  concluded  that  it  was  the  ganglia   of  the 


202  A  ction  of  the  Bile  A  cids 

heart  and  not  the  vagi  that  were  acted  on  by  the  biHary 
acids.* 

Landois  asserts  that  the  first  action  of  the  bile  acids 
is  to  increase  the  number  of  the  heart  beats.  It  is  true 
that  many  poisons,  have  at  first  the  action  contrary  to 
that  for  which  they  are  best  known.  Landois  used  only 
very  dilute  solutions,  such  as  lo  C.C.  of  a  2  per  cent. 
solution  of  bile  acids  diluted  with  90  C.C.  of  distilled 
water.  He  found  that  in  frogs,  rabbits,  and  cats,  the 
first  result  of  the  injection  of  the  bile  or  bile  acids  into 
the  heart  was  an  increase  in  the  number  of  beats. f 

Leyden  noticed  also  in  the  cut-out  heart  of  the  frog 
an  increase  of  the  beats  from  11  to  15,  and  even  to  24 
in  the  quarter  minute. J  In  my  own  experiments  on 
the  frog,  I  invariably  noticed  a  slight  rise,  from  g  in  the 
quarter  minute  to  10  or  11,  and  these  experiments  were 
made,  without  disturbing  the  heart,  by  the  injection  of 
bile  acid  solution  under  the  skin. 

Traube,  however,  considered  that  Landois  was  alto- 
gether wrong  in  saying  that  small  doses  of  the  bile 
acids  increase  the  beats  of  the  pulse,  while  large  ones 
decrease  them.  The  difference  depends  upon  the  state 
of  the  regulating  system,  whether  it  be  in  greater  or 
less  activity.  If  this  system  be  active,  there  is  seen 
after  injection  of  the  bile  acids  a  lowering  of  the  blood 
pressure  with  a  considerable  rise  in  the  number  of  the 
pulse.  If  the  activity  of  the  spinal  part  of  the  regu- 
lating system  be  removed,  then  there  is  a  decrease  in 
the  beats  of  the  pulse.  The  bile  acids  when  injected 
into  the  jugular  vein  at  once  meet  with  and  destroy,  or 
injure,  a   certain   number  of  red  corpuscles;    then  the 


*  "Rbhrig,  Arch,  dcr  Hcilkundc,  I'iQi,^.  Z^S-     There  is  also  an   Inaugural   Dis- 
sertation,   Uebcr   den   EiuJIkss  dcr  Galle  auf  dcr  Hcrzthatigkeit,   Leipzig,  1863, 
hich  I  have  not  been  able  to  see. 
f  Landois,  Deutsche  Klinik].  1863,  p.  449. 
X  Leyden,  op.  cit.  p.  93. 


upon  the  Heart.  203 

blood  containing  these  dissolved  red  corpuscles  and  the 
bile  acids  is  quickly  carried  through  the  right  side  of 
the  heart  into  the  lungs.  The  red  corpuscles  being 
dissolved  can  no  longer  act  as  the  carriers  of  oxygen, 
and  the  blood  is  brought  by  the  pulmonary  veins  to  the 
left  side  of  the  heart  and  distributed  to  the  coronary  ar- 
teries ;  this  blood  is  incapable  of  exchanging  oxygen 
with  the  muscular  walls  of  the  heart,  and  they  are 
therefore  injured,  and  in  this  way  a  slow  pulse  is  seen.* 

About  the  same  time  Johannes  Ranke  arrived  at  the 
conclusion,  somewhat,  similar  to  that  of  Traube,  that 
the  bile  acids  have  a  paralysing  influence  upon  striped 
muscular  tissue.  To  the  influence  of  the  bile  acids 
upon  the  muscular  fibres  of  the  heart  the  slow  pulse  is 
therefore  due.f 

The  statements  as  to  the  cause  of  the  slow  pulse 
being  thus  so  contradictory,  I  attempted  a  few  years 
ago  a  research  upon  this  subject,  the  results  of  which 
were  laid  before  the  Royal  Society. J  The  first  element 
which  it  was  necessary  to  eliminate  was  the  influence 
of  the  vagus ;  and  thanks  to  von  Bezold's  discovery,  a 
ready  means  in  atropine  was  at  hand,  by  which  the  in- 
hibitory function  could  be  removed. 

The  heart  of  the  frog  lends  itself  very  readily  to  all 
researches  of  this  kind ;  if  arranged  in  a  Bowditch's 
apparatus,  the  circulation  can  be  readily  kept  up  for 
hours,  if  fed  by  serum  ;  and  if  the  aorta  be  connected 
with  a  manometer,  the  number  and  force  of  the  pulsa- 
tions of  the  heart  can  be  easily  registered. 

*  Traube,  Berlin,  klin.  Wochenschriff,  1864,  p«86,  and  Gesammelte  Beitrdge, 
Berlin,  1871,  Bd.  i.  p.  366. 

f  Johannes  Ranke,  Arch.  f.  Anat.  Phys.  ti.s.w.  1864,  p.  340 :  also  in  Tetanus, 
Leipzig,  1865,  p.  395.     See  his  experiments  above,  p.  igg. 

+  Wickham  Legg,  Proceedings  of  the  Royal  Society  of  London,  1S76,  Vol.  xxiv. 
p.  442. 


204 

Fig.  I. 


Action  of  the  Bile  Acids 


Fig.  2. 


Fig.  3. 


Fig.  4. 


Normal    tracing 
of  frog's  heart. 


Tracing  under  influence 
of  atropine. 


First  effect  of  the  bile 
acid  salts. 


Later  effect  of  the  bile 

acid  salts. 
(The  cylinder  having 
been  reversed,  the  trac- 
ing must  be  read  in  a 
direction  opposite  to  the 
other  three). 


upon  the  Heart. 
Frog's  Heart  in  Bowditch's  Apparatus. 


205 


Time  in 
Seconds. 

Number  of 
Pulsations. 

Height  of  Curve 
in  millimeters. 

Remarks. 

130 

31 
32 
38 

6 

4 

See  Fig  i. 

Curves  double  topped. 

" 

31 

6 

Atropia  introduced  into  the  serum,  so  that 
it  contained  -028  per  cent.    (See  Fig.^.) 

120 

24 

7 

Bile  acids  introduced  into  the  serum. 

» 

16 

7 

Records  in  continuous  30  seconds.  (See  Fig.  3.) 

1) 

16 

8 

Pulse  now  goes  in  pairs,  6'S  seconds  between 
each  pair  of  pulsations :  between  the  pulses 
of  each  pair  3-2  seconds. 

:; 

16 
16 
16 

8-5 

9 

8 

These  do  not  go  in  pairs. 
These  go  in  pairs. 

130 

13 

12 

A  great  change  in  character  of  curves.  Sys- 
tole TtaiChes  maximum  height  in  I'j  seconds. 
They  slowly  sink,  scarcely  meeting  abscissa 
until  the  next  contraction  begin.  They  are 
nearly  all  alike.  One  takes  up  23  mm. 
others  38  mm.   (See  Fig.  4.) 

>) 

12-5 

10 

Immediately  after  the  heart  ceases  to  beat. 
No  contractions  upon  electrical  irritation. 

Four  other  like  experiments,  with  a  Hke  result,  were 
made  in  December,  1872,  and  January,  1873.  In  one 
of  them  the  bile  acids  were  added  to  the  serum  first 
and  the  atropine  added  afterwards ;  but  the  same  re- 
sults were  attained.  The  slowness  of  the  pulse  arose 
as  before,  and  was  unchanged  by  the  addition  of  the 
atropine. 

Another  series  of  experiments  on  the  irritability  of 
the  vagus  was  made. 

The  heart  and  right  vagus  of  a  frog  laid  bare,  the 
heart  beating  12  in  15  seconds.  The  vagus  was  then 
irritated  by  induced  electricity  and  the  heart  stood  still 
in  diastole.  Three  or  four  drops  of  the  solution  of 
atropia  of  the  British  Pharmacopoeia  were  now  let  fall 
upon  the  heart.  After  five  minutes  the  beats  were  7  in 
15  seconds.  The  right  vagus  was  then  again  irritated 
by  induced  electricity  with  no  change  in  the  heart. 
After  10  minutes,  four  drops  of  a  10  per  cent,  solution  of 
bile  acids  were  let  fall  upon  the  heart  and  neighbour- 
hood.    Thereupon,  for  nearly  a  minute,  the  heart  beats 


2o6  A  ction  of  the  Bile  A  cids 

rose  to  TO  in  15  seconds,  but  directly  after  fell  to  6  in 
15  seconds,  the  right  vagus  was  again  irritated  but  no 
change  followed.  Three  minutes  after,  the  beats  were 
5  in  15  seconds.     The  experiment  was  then  broken  off. 

Two  other  experiments  were  made  with  like  results. 
They  would  seem  to  show  that  the  bile  acids  do  not 
restore  to  the  vagti^s  the  inhibitory  power  destroyed  by 
the  atropia. 

With  mammals  I  have  attained  like  results. 

If  the  inhibitory  action  of  the  vagus  can  therefore  be 
excluded,  there  remain  two  other  factors  as  a  cause  of 
the  slow  pulse,  the  muscular  walls  and  the  ganglia  of 
the  heart. 

To  deal  first  with  the  muscular  walls,  to  the  failure 
of  which  both  Traube  and  Johannes  Ranke  attribute 
the  slow  pulse. 

It  has  already  been  shown  (p.  198.)  that  the  bile 
acids  have  no  physiological  action  upon  striped  muscu- 
lar tissue,  although  they  have  a  marked  chemical  action 
when  injected  into  muscles.  Have  they,  then,  any 
chemical  influence  upon  the  ventricle  ?  To  test  this 
supposition,  I  thought  of  making  some  experiments 
upon  the  action  of  the  bile  acids  on  the  ventricle  when 
separated  from  the  rest  of  the  heart. 

It  is  commonly  said  that  the  ventricle  of  the  frog's 
heart  continues  to  beat  for  some  time  after  it  be  severed 
from  the  auricles.  I  found,  however,  that  the  time  was 
not  long  enough,  nor  the  beating  of  the  ventricle  constant 
enough,  to  enable  me  to  judge  of  the  difference  in  time 
taken  to  bring  the  ventricle  to  a  standstill  if  immersed  in 
serum,  or  in  serum  containing  i  prr  cent,  of  bile  acids.  I 
fell  back  therefore  on  a  method  employed  by  Luciani*  in 
Ludwig's  Laboratory.  It  consists  in  introducing  into 
the  ventricle  of  the  frog's  heart,  a  tube  divided  verti- 
cally by  a  septum,  and  tying  the  ventricle  on  to  the 

*  Luciani,  Arbcitcn  aits  dent  phys.  AnstaU  zn  Leipzig,  1873,  Jahrg.  vii.  p.  120. 


upon  the  Heart.  207 

cannula  below  the  auricles.  The  heart  is  supplied  by 
serum  through  the  double  cannula  and  each  pulsation 
is  recorded  by  a  manometer.  I  made  five  of  these  ex- 
periments, but  I  could  detect  no  change  in  the  alternate 
periods  of  rest  and  of  contractions,  as  described  by 
Luciani,  after  the  introduction  of  bile  acids  in  i  per  cent. 
into  the  serum,  nor  after  the  removal  of  the  bile  acid 
serum  and  the  feeding  of  the  heart  with  pure  serum. 
Both  before  and  after  the  use  of  the  bile  acids  the  con- 
tractions of  the  ventricle  were  alike.  It  would  seem, 
therefore,  that  the  bile  acids  have  no  action,  either 
chemical  or  physiological,  upon  the  ventricle  of  the 
frog's  heart  separated  from  the  auricles. 

If,  then,  the  bile  acids  have  no  influence  upon  the 
ends  of  the  vagus  in  the  heart,  nor  upon  the  muscular 
tissue,  there  remains,  in  the  present  state  of  knowledge, 
only  one  other  cause  of  the  heart's  movement  which 
may  beget  a  slow  pulse ;  the  ganglia  of  the  heart. 
How  these  are  affected  by  the  bile  acids  there  is  no 
direct  evidence  to  show.  I  do  not  know  of  any  means 
by  which  these  ganglia  can  be  put  out  of  play ;  and 
thus  immediate  proof  that  the  ganglia  are  concerned  is 
wanting.  But  if  an  argument,  per  viam  exclicsionis,  be 
allowed,  then  it  must  be  that  the  slow  pulse  is  due  to 
the  action  of  the  bile  acids  upon  the  cardiac  ganglia. 

I  only  became  acquainted  with  the  observations  of 
J-.  Steiner  a  few  months  ago.  He  finds,  as  I  do,  that 
the  slow  pulse  is  not  due  to  the  excitement  of  the  ends 
of  the  vagus,  as  the  slow  pulse  appears  after  atropia 
has  been  given.  But  he  has  also  made  an  observation 
of  much  interest.  If  bile  be  let  fall  upon  the  back  sur- 
face of  the  frog's  heart,  there  is  at  once  a  fall  in  the 
pulse,  or  even  complete  cessation  of  the  heart's  beats. 
But  if  the  bile  only  touch  the  fore  surface  of  the  heart 
there  is  no  change  in  the  pulse  for  10  minutes.  Further, 
if  the  ventricle  were  cut  off  after  Stannius'  ligature  were 


2o8  A  ction  of  the  Bile  A  cids 

applied,  the  sinus  still  beat ;  but  if  touched  with  bile, 
the  sinus  at  once  ceased  to  pulsate.  Again,  if  the 
Stannius'  ligature  were  applied  to  the  heart,  the  sinus 
taken  away  and  the  ventricle  cut  off,  the  auricle  still 
beat,  and  continued  to  beat  after  it  was  touched  with 
bile,  though  after  some  time  the  number  of  pulsations 
became  less. 

Steiner  thinks  that  it  is  proved  that  the  bile  acts  upon 
only  one  of  the  ganglia  of  the  heart,  that  in  the  sinus, 
and  not  on  the  atrio-ventricular  ganglia.* 

On  the  hearts  of  snails.  It  has  been  asserted  that  the 
heart  of  the  snail  shows  no  nervous  elements.  I  have 
made  a  number  of  experiments  on  the  action  of  the  bile 
acids  upon  the  heart  of  this  animal,  but  I  have  per- 
ceived no  change  worthy  of  note.  The  bile  acids 
seemed  to  have  no  influence,  neither  increasing  nor 
decreasing  the  number  of  pulsations,  which  are  always 
very  irregular. 

On  the  lymphatic  hearts  of  frogs.  Rohrig  has  made 
some  observations  on  the  influence  of  the  bile  acids  on 
the  lymphatic  hearts  of  the  frog.  Both  hearts  were 
laid  bare,  and  six  drops  of  a  5  per  cent,  solution  of  gly- 
cocholate  of  soda  spread  upon  the  muscular  tissue. 
Before  the  bile  acids,  the  number  of  beats  was  12  in 
15  seconds;  one  hour  after,  10  beats;  two  hours,  8; 
three  hours,  6  ;  four  hours,  4.  At  the  end  of  four  hours 
the  least  number  of  beats  was  attained,  and  at  the  end 
of  six,  the  usual  number  was  again  seen. 

Rohrig  thinks  that  the  action  of  the  bile  acids  upon 
the  lymph  heart  runs  parallel  with  that  upon  the  blood 
heart ;  though  with  small  doses  the  lymphatic  hearts 
may  cease  to  act  after  a  few  hours,  while  the  systemic 
heart  is  still  beating,  and  the  frog  shows  no  change."]" 

My  own  observations  lead  to  a  conclusion  altogether 

•  J.  Steiner,  Arch.f.  Anat.  Phys.  u.s.w.  1874,  p.  474. 
f  Rohrig,  Arch.  d.  Heilkundc,  1863,  p.  418. 


on  the  Blood  Pressure.  2og 

different  from  that  of  Rohrig.  And  perhaps  I  may  be 
allowed  to  say  that  I  somewhat  regret  my  own  results, 
as,  if  the  bile  acids  had  shown  a  distinct  action  on  the 
lymphatic  heart,  it  would  have  been  an  important  aid 
to  the  proof  that  the  cause  of  the  slow  pulse  is  nervous. 
I  made  six  observations,  and  in  no  case  found  the  rate 
of  the  pulsation  of  the  lymphatic  hearts  changed  soon 
after  the  administration  of  the  bile  acids  by  subcutane- 
ous injection.  The  lymphatic  heart  only  began  to  beat 
more  slowly  when  general  death  was  setting  in  from 
the  action  of  the  poison.  The  systemic  heart,  on  the 
contrary,  shows  the  action  of  the  poison  within  a  few 
minutes  of  its  injection,  and  the  pulsations  may  sink 
from  13  to  3  in  the  15  seconds  in  seven  minutes  after 
the  injection  of  i  C.C.  of  a  10  per  cent,  solution  of  bile 
acid  under  the  skin. 

I  give  the  details  of  one  experiment.  On  Dec.  24th. 
the  right  posterior  lymphatic  heart  was  exposed  at  10.55 
a.m.  The  pulsations  vary  from  7  to  g  in  15  seconds.  At 
II. 5  the  average  is  g  in  15  seconds.  At  11. 5  one  C.C. 
of  a  10  per  cent,  of  bile  acids  was  injected  under  the 
.skin  of  the  neck. 


II. 12  a.m. 

10  in  15  seconds. 

12.20  p.m.  another  injection. 

II. 15      ;; 

9 

12.25     „      II  in  15  seconds. 

11.20  „ 

9 

12.31     „      10     „ 

11.24  „ 

struggles. 

Lymphatic  heart  now  ceased 

11.28  „ 

9 

to  act. 

12  noon 

10 

2  p.m.  animal  found  dead. 

On  the  blood-pressure.  Traube  first  called  attention 
to  the  action  of  the  bile  acids  on  the  blood-pressure. 
He  found  that  if  an  animal  be  rendered  motionless  with 
woorara,  and  a  bile  acid  soda  salt  be  injected  into  the 
jugular  vein,  not  towards  the  heart,  but  towards  the 
head,  the  blood -pressure  is  much  decreased  and  the 
pulse  increased  in  frequency.  If  the  dose  of  woorara 
have  been  large,  the  same  results  are  obtained  as  those 

p 


210  Influence  of  the  Bile  Acids 

seen  after  division  of  the  vagi:  great  decrease  in  the 
number  of  the  pulse  and  in  the  blood-pressure.  In 
both  cases,  however,  there  follows  either  an  increase 
or  a  decrease  of  the  frequency  of  the  pulse  ;  and,  at 
the  same  time,  a  rise  in  the  blood-pressure. 

There  is  a  great  difference,  too,  according  to  the 
vessel  into  which  the  injection  is  made.  An  injection 
into  the  carotid  will  completely  remove  the  effects  of 
an  injection  into  the  jugular.  For  example,  if  the  vagi 
be  divided,  and  the  bile  acid  salts  injected  into  the 
jugular  vein,  there  is  a  lowering  of  the  blood-pressure 
and  a  decrease  in  number  of  the  pulse.  If,  while  the 
pulse  and  the  pressure  are  sinking,  another  dose  be 
injected  into  the  carotid,  the  pulse  and  pressure  at  once 
begin  to  rise.  If  a  similar  experiment  be  made  while 
the  vagi  are  undivided,  there  are  seen,  after  injection 
into  the  vein,  lowering  of  the  blood-pressure  and  increase 
in  the  number  of  the  pulse  ;  if,  while  these  phaenomena 
are  still  showing  themselves,  an  injection  be  made  into 
the  carotid,  there  is  increase  of  the  blood-pressure  and 
lowering  of  the  pulse.* 

Kemarsky  found  that,  with  animals  under  the  influ- 
ence of  woorara,  there  was  a  fall  in  the  blood-pressure. 
This  fall  is  caused  solely  by  the  action  of  the  bile  acids 
on  the  heart,  as  if  both  vagi  and  spinal  chord  be  divided 
the  fall  is  still  seen.  If  the  vagi  be  not  divided  there  is 
an  increase  in  the  number  of  the  heart  beats  ;  if  divided, 
the  pulse  becomes  slow,  so  that  Kemarsky  thinks  the 
slow  pulse  due  to  the  action  of  the  vagus.'\ 

I  have  myself  made  some  observations  with  the  kymo- 
graph on  the  blood-pressure  as  affected  by  the  injection 
of  the  bile  acid  salts  into  the  blood  ;    but  in   some   re- 

*  Traube,  Berlin,  kiln.  Wochenschrlft,  1864,  pp.  86  and  147.  Also  in  his 
Gesaiiuncltc  Beitrdge,  Berlin,  187 1,  Bd.  i.  p.  366. 

f  Kemarsky,  jfahrcsbcylchtc  uebcr  die  Forlsclirlttc  d.  Anat,  u.  Phys.f.  1875,  Bd. 
iv.  p.  171.  Reasons  for  not  accepting  tliis  conclusion  of  Kemarsky  as  to  the  vagi 
have  been  given  above,     (p.  205.) 


on  the  Blood  Pressure.  211 

spects  I  have  not  attained  the  same  results  as  those  of 
Traube. 

April  30th.    A  middle-sized  rabbit,  kymograph  in  con- 
nexion with  the  carotid  artery. 


Time 

Pulse  in  15 

Blood-pressure 

SECONDS 

IN    MILLIMETERS 

r   67 

I  10 

Normals 

70 

126 

I   72 

116 

12.    59'  50"  p.m.      Injection    of    i 

C.C.  of  a  12  per  cent,  solution  of 

Platner's  crystallised  bile  into  the 

external  jugular  vein  towards  the 

heart. 

I.  0'  11".      Injection  ended.     From 

12.   59    50"  to   12,   59'  58"  there 

71 

108 

'  were  40  beats  of  the  heart ;  from 

this  time  to   i,  0'   11"  there  were 

52  pulsations,  and  the  blood-pres- 

sure began  to  fall  immediately. 

6s 

78          • 

I.  0'  19"  -6 

61 

84 

1 .  0'  34"  -6 

58 

90 

I.  i' 

62 

94 

1-3' 

-  68 

106 

In  this  experiment  it  will  be  seen  that  an  injection  of 
the  bile  acid  salts  into  the  jugular  vein  towards  the 
heart  was  quickly  followed  by  a  fall  both  in  the  blood- 
pressure  and  the  number  of  the  pulse,  though  accord- 
ing to  Traube  there  should  be  a  fall  in  the  pressure  and 
an  increase  in  the  pulse. 

In  another  experiment  on  a  rabbit  the  only  effect 
noted  was  an  elevation  of  the  blood-pressure  slight  and 
rapidly  passing  away. 

April  28th.  Black  rabbit,  large.  Kymograph  in 
connexion  with  carotid  artery.     Pulse  not  counted. 

Time  Blood-pressure 

IN  millimeters 

3.  25'  92 

3.  28'  98 

P  2 


212  Influence  of  the  Bile  Acids 

Time  Blood-pressure 

in  millimeters 

3.  29'  15'            Injection  of  i    C.C.  of  a  10  per  cent.  98 
solution    of   Platner's  crystallized 
bile  into  the  right  external  jugular 
towards  heart. 

3.  29'  45"           Injection  over  96 

3-  20'  55"  104 

3.  30'  98 

3-  30'  45"  100 

3-  32'  100 

3.  33'  104 

3.  34'  106 

A  clot  now  formed  and  the  artery  ceased  to  record. 

In  all  the  other  experiments  which  I  have  made  I 
have  noticed  a  fall  in  the  blood-pressure  after  the  injec- 
tion of  the  bile  acid  salts  into  the  jugular  vein.  I  have 
been  somewhat  surprised  at  the  little  effect  which  one, 
two,  and  three  C.C.  of  a  ten  per  cent,  solution  of  bile  acid 
salts,  have  when  injected  into  the  jugular.  On  the  other 
hand,  the  same  dose  injected  into  the  carotid  causes 
at  once  marked  symptoms,  with  a  considerable  rise  in 
the  blood-pressure.  The  blood-pressure  sinks  during 
the  injection,  but  at  once  begins  to  rise  somewhat 
irregularly  and  keeps  high  for  a  few  seconds.  It  then 
falls,  and  comes  to  an  end  with  the  death  of  the  rabbit. 

The  peculiar  symptoms  seen  on  injection  into  the 
carotid  are  described  immediately  below. 

On  the  Respiration.  A  very  curious  appearance  after 
the  injection  of  the  bile  acids  into  the  carotid  was  first 
noticed  by  Traube  ;  a  spasm  of  the  respiratory  muscles 
takes  place,  and  the  diaphragm  is  held  in  deep  inspira- 
tion. Apncea  follows,  but  the  heart  still  beats.  If  arti- 
ficial respiration  be  practised,  the  animal  can  be  kept 
alive.  If  only  small  doses  be  given,  there  is  a  great 
fall  in  the  number  of  respirations,  even  to  2  in  a 
minute.*     Leyden  has  repeated  these  experiments. f 

*  Traube,  Berlin,  klin.  Wochcnschrift,  1864,  p.  147.     Also  in  Gcsamm.  Beitrage, 
Berlin,  1871,  Bd.  i.  p.  378. 

t  Leyden,  BeilMge  ziir  Pathologie  des  Icterus,  Berlin,  1866,  p.  70. 


on  the  Respiratiofi  mid  Nervous  System.  213 

The  inspiratory  spasm  is  very  well  marked,  as  I  can 
testify  from  my  own  observations  ;  and  it  persists  in  the 
rabbit  even  after  the  removal  of  all  the  cerebrum  above 
the  tentorium,  except  the  corpora  quadrigemina.  After 
their  removal,  the  spasm  is  no  longer  well  marked. 

Mr.  Graham  Brown  found  that  the  respirations  of 
rabbits  were  perceptibly  decreased  in  rapidity  after  the 
injection  of  the  bile  acids  under  the  skin.*  Albers 
noted,  20  minutes  after  pure  glycocholic  acid  had  been 
placed  under  the  skin  of  frogs,  that  the  breathing  was 
quicker  ;  later  on  dyspnoea. f 

On  the  Nervous  System.  It  has  already  been  noted 
that  epileptiform  convulsions,  and  tetanus  have  followed 
the  injection  of  bile,  even  if  filtered,  into  the  veins.  The 
same  phaenomena  have  followed  the  injection  of  the 
pure  bile  acid  salts.  It  is  thus  probable  that  the  bile 
acids  in  the  filtered  bile  are  the  active  agents  in  causing 
the  nervous  symptoms. 

Theodor  von  Dusch  noted  these  tetanic  symptoms 
and  opisthotonos,  followed  by  sudden  death,  after  the 
injection  of  solutions  of  glycocholate  of  soda  and  of 
taurocholate  of  soda  into  the  jugular  vein.  A  large 
amount,  8  and  16  C.C.  of  a  20  per  cent,  solution  of  gly- 
cocholate of  soda,  could  be  injected  into  the  vena  saphena 
of  a  dog  without  causing  more  than  passing  symptoms. 
After  death,  the  lungs  were  found  full  of  haemorrhages, 
the  right  side  of  the  heart  filled  with  clotted  blood  ;  the 
left  empty ;  while  the  vena  cava  inferior  was  distended 
with  blood. J  Similar  observations,  though  less  mi- 
nutely detailed,  have  been  recorded  by  nearly  every 
other   observer   who    has    experimented   with   the    bile 


*  J.  Graham  Brown,  Proceedings  of  the  Royal  Society  of  Edinburgh,  1875, 
vol.  viii.  p.  527. 

f  J.  F.  H.  Albers,  Arch.  f.  path.  Anat.  1862,  Bd.  xxiii.  p.  582. 

X  Th.  von  Dusch,  Untcrstichungcn  und  Experimente  also  Beitrag  zur  Pathogcnese 
dcs  Icterus,  Leipzig,  1854,  pp.  18  ct  seqq. 


214  Thrombosis  of  the  Pulmonary  Artery 

acids,  such  as  Frerichs,*  Kiihne,t  Leyden,J   Feltz  and 
Ritter.§ 

At  the  time  at  which  Theodor  von  Dusch  wrote,  the 
doctrine  of  thrombosis  of  the  puhnonary  artery  was  less 
widely  spread  than  at  present,  and  it  is  hardly  surpris- 
ing that  he  failed  to  draw  the  conclusions,  which  now 
seem  to  lie  on  the  surface.  Johannes  Ranke  and 
Baldauf,  indeed,  apparently  without  being  acquainted 
with  Theodor  von  Dusch's  observations,  have  come  to 
the  conclusion  that  the  sudden  death  is  due  to  throm- 
bosis of  the  pulmonary  artery.  ||  The  blueness  of  the 
lips,  the  tetanic  convulsions,  the  expulsion  of  the  urine 
and  faeces,  after  death  the  distension  of  the  right  side  of 
the  heart  and  the  vessels  leading  into  it,  the  right  side 
being  sometimes  filled  with  clots, ^  the  pulmonary  hae- 
morrhages, and  the  emptiness  of  the  arteries,  all  noted 
by  von  Dusch,  make  the  case  a  typical  one  of  death 
from  pulmonary  embolism.  The  explanation  which 
Johannes  Ranke  gives  of  the  formation  of  the  thrombosis 
is  very  probable.  The  bile  acids  dissolve  the  red  cor- 
puscles ;  as  a  consequence  of  the  solution  of  the  red 
corpuscles,  a  clot  immediately  forms,  which  is  carried 
to  the  heart  or  into  the  pulmonary  artery.  And  this 
explains  the  fact  noted  by  Th.  von  Dusch  that  when 
the  injection  was  made  into  a  vein  at  a  distance  from 
the  heart,  such  as  the  crural  or  saphena,  sudden  death 
did  not  always  take  place.**  Johannes  Ranke  found 
after  the  same  experiment  that  the  vena  cava,  as  high 
as  the   liver,  was  filled  with  a  thrombus,  while  many  of 

•  Frerichs,  Klinik  d.  Leberkrankhciten,  Braunschweig,  1858,  Bd.  i.  p.  404. 

f  Kiihne,  Arch.  f.  path.  Anat.  1858,  Bd.  xiv,  p.  326. 

J  Leyden,  op.  cit.  p.  72. 

§  Feltz  and  Ritter,  Jojiriial  dc  r Anatomic  et  de  la  physiologic,  1874,  t.  x.  p.  571. 

II  Johannes  Ranke,  Die  Blutvcrtheilung  tind  der  Thdtigkcitswechscl  der  Orga/ic, 
Leipzig,  1871,  p.  164. 

U  Th.  von  Dusch  says  that  he  found  a  thrombus  in  a  large  pulmonary  vein 
(p.  21).     This  is  probably  an  error  of  observation  for  pulmonary  artery. 

*•  See  the  older  observations  with  this  same  result,  p.  118. 


is  the  Cause  of  Death.  215 

the  smaller  branches  of  the  pulmonary  artery  were  also 
filled  with  clots. 

Johannes  Ranke  states  that  the  dose  of  the  bile,  or 
the  bile  acid  salts,  which  is  enough  to  cause  death  in 
rabbits,  is  only  fifteen  milligrammes.  I  do  not  think  that 
this  is  always  the  case.  I  have  injected  50,  200,  and 
even  800  milligrammes  of  Platner's  crystallized  bile  in 
10  per  cent,  solution  into  the  jugular  veins  of  rabbits,  in 
different  individuals,  without  causing  thrombosis  of  the 
pulmonary  artery  or  of  the  right  heart.  No  obvious 
effect  was  caused  by  the  injection  of  50  or  200  milli- 
grammes. But  after  the  dose  of  800  milligrammes,  the 
pulse  and  respiration  at  once  fell,  and  the  rabbit  ap- 
peared to  be  dying  ;  it  was  killed  at  once  by  opening 
the  chest  ;  the  heart  was  found  still  feebly  contracting 
on  the  right  ventricle  and  auricle  ;  but  none  on  the  left 
side.  Irritation  of  the  ventricles  with  Pulvermacher's 
forceps  called  forth  no  contractions  ;  but  the  same  irri- 
tation to  the  phrenic  nerve  caused  violent  contractions  of 
the  diaphragm.  Direct  irritation  of  the  muscles  of  the 
thigh,  and  of  the  anterior  crural  nerve  was  followed  by 
marked  contractions.  Heart  and  pulmonary  artery  fol- 
lowed with  a  fine  pair  of  scissors,  but  no  clots  were 
found.  Urine  from  the  bladder  was  turbid  and  straw- 
coloured,  but  showed  no  reaction  with  nitric  acid. 

Probably  the  difference  in  observation  is  due  to  a 
difference  in  the  food  of  the  animals ;  and  the  difference 
between  the  older  experiments  spoken  of  above,  must 
be  explained  on  the  same  grounds,  or  a  difference  in 
the  constitution  of  the  blood. 

Huppert  injected  3-3  grm.  of  glycocholate  of  soda, 
dissolved  in  20  C.C.  of  water,  into  the  jugular  vein  of  a 
dog,  and  found  that  the  creature,  up  to  that  moment 
very  restless,  became  quiet,  and  fell  into  a  sleep  from 
which  he  could  hardly  be  aroused.*     In  the  same  way, 

*  H.  Huppert,  Arch.  d.  Hcilkunde,  1864,  p.  241. 


2i6  InHnence  of  the  Bile  Acids 

Mr.  Graham  Brown  noticed  much  drowsiness,  ending 
at  last  in  coma,  after  the  injection  of  the  bile  acids 
under  the  skin  of  rabbits.  No  convulsions  were  no- 
ticed ;  nor  did  the  pupil  show  any  change.*  Albers 
speaks  of  convulsions  and  other  nervous  symptoms, 
after  pure  glycocholic  acid  had  been  introduced  under 
the  skin  of  frogs. "j"  Leyden  does  not  think  that  the  bile 
acid  salts  are  a  direct  irritant.  When  the  sciatic  nerve 
of  a  fros:  with  the  muscles  still  attached  to  it  was  laid 
in  bile,  no  contractions  of  the  muscles  appeared. J  I 
have  no  doubt  of  the  action  of  the  bile  acid  salts  as 
narcotics.  When  moderate  doses  are  given  to  frogs, 
the  animals  shortly  become  torpid,  insensible  to  all 
stimulus,  showing  no  reflex  action  whatever.  They  lie, 
with  contracted  pupils,  as  if  in  a  deep  sleep. 

I  have  made  some  observations  upon  the  changes  in 
the  reflex  movements  which  follow  the  administration  of 
bile  acid  salts.  Out  of  five  experiments,  nearly  all 
alike,  I  give  the  details  of  one. 

Dec.  ig.  The  anterior  cerebral  hemispheres  of  a  frog 
were  removed,  the  optic  thalami  being  left  uninjured. 
The  foot  of  the  frog  was  irritated  by  being  plunged  in 
water,  made  just  perceptibly  acid  to  taste  by  sulphuric 
acid. 

The  numbers  represent  the  time  in  seconds  which 
passed  between  the  plunging  of  the  foot  into,  and  its 
withdrawal  from,  the  water  with  which  it  was  irritated. 

12.22  p.m.     12,  6,  7,  8,  6,  7,  6. 

12.32  p.m.  "5  C.C.  of  a  10  per  cent,  solution  of  bile 
acids  injected  under  the  skin  of  the  back. 

12.39  p.m.       I,  2,  I,  I,  29,  27,  15,  16,  21,  28,  22,   26. 

I  p.m.     The  head  was  cut  off. 

1.25  p.m.     9,  9,  9,  9,  10,  10,  10. 

*  J.  Graham  Brown,  Proceedings   of  the  Ruyal  Society  of  Edinburgh,    1875, 
Vol.  vi.i.  p.  530. 

f  J.  F.  H.  Albers,  Arch.  f.  path.  Anat.  1862,  Bd.  xxiii.  p.  582. 

+  Leyden,  Belirdge  znr  Pathologic  dcs  Icterus,  Berlin,  1866,  p.  95. 


07t  the  Temperature  and  Urine.  217 

In  all  cases  a  minute  passed  between  the  application 
of  the  irritant ;  and  the  foot  was  well  washed  with  dis- 
tilled water  after  each  observation. 

It  would  appear  that  the  reflex  irritability  is  decreased 
by  the  action  of  the  bile  acids  ;  a  statement  in  which 
Kemarsky  also  joins.* 

Upon  the  serous  membranes.  It  is  well  known  that  an 
escape  of  bile  into  the  peritonaeum  is  an  almost  fatal 
accident,  peritonitis  being  at  once  set  up.  This  pro- 
perty of  the  bile  would  seem  to  be  due  to  the  presence 
of  the  bile  acid  salts,  as  the  same  violent  peritonitis 
follows  the  injection  of  these  salts  into  the  peritonaeum. 

On  the  temperature.  Rohrig  was  struck  by  the  cold- 
ness of  the  animals  poisoned  by  the  bile  acid  salts,  and 
found  their  temperature  much  lower  than  natural. f 
Feltz  and  Ritter  also  speak  of  a  low  temperature  as 
a  result  of  poisoning  by  the  bile  acids. J  Kemarsky 
found  the  temperature  to  be  lowered  in  direct  propor- 
tion to  the  amount  of  bile  acid  salts  injected  into  the 
blood  ;  an  inconsiderable  rise  of  temperature  preceded 
the  fall.§  Huppert,  in  two  dogs,  found  very  little 
change  ;||  the  thermometer  in  the  rectum  being  con- 
stant at  37°  -6  C.  or  37°  '8  C.  (g9°-6  F.  or  100°  F.) 

Rohrig  goes  so  far  as  to  propose  the  bile  acids  as  a 
remedy  in  fever  to  bring  down  the  temperature.  It  is 
possible,  however,  that  the  lowering  of  the  temperature 
is  not  due  to  a  specific  action  of  the  bile  acids,  for  many 
poisons  cause  a  fall  in  the  temperature  some  hours  be- 
fore they  put  an  end  to  life. 

On  the  Urine.  After  the  injection  of  the  bile  acid 
salts   into  the  blood,  the  urine  quickly  becomes  high- 

*  Kemarsky,  Jahresbcrichte  neher  die  Fortschritte  d.  Anat.  u.  Phys.  f.  1875,  Bd. 
iv.  p.  171. 

f  Rohrig,  Arch.  d.  Hcilkimdc,  1863,  p.  394. 

J  Feltz  and  Ritter,  Journal  dc  VAnatomie  et  de  la  Physiologic,  1874,  t.  x.  p.  576. 

§  Kemarsky,  jfahrcsbcrichte  ucbcr  die  Fortschritte  d.  Anat.  u.  Phys.  /.  1875,  Bd. 
iv.  p.  171. 

II  H.  Huppert,  Arch.  d.  Heilkimde,  1864,  p.  241. 


2i8  Physiological  Action  of  the  Bile  Acids 

coloured  from  the  presence  of  haemoglobin.  No  red 
blood  corpuscles  can  be  found,  but  abundance  of  casts 
of  the  urinary  tubules,  with  dark  granules.  So  far  all 
observers  are  agreed.  But  Frerichs  announced  that  in 
the  urine  is  also  to  be  found  bile  pigment ;  and  he  ex- 
plains the  presence  of  the  bile  pigment  by  a  metamor- 
phosis in  the  circulation  of  the  colourless  bile  acid  salts 
into  pigment.*  Kiihne  found  bile  pigment  in  the  urine 
after  the  injection  of  bile  acids  into  the  circulation,  but 
apparently  attributed  the  presence  of  the  pigment  to  the 
setting  free  of  haemoglobin  into  the  plasma. t 

I  have  myself  been  unable,  in  numerous  experiments, 
to  satisfy  myself  of  the  presence  of  bile  pigment  in  the 
urine  of  rabbits  after  the  injection  of  the  bile  acids  into 
the  blood.  I  am  inclined  to  believe  that  the  difference 
in  observation  is  due  to  the  animals  experimented  upon. 
The  urine  of  dogs  often  shows  a  Gmelin's  reaction, 
when  the  animals  are  believed  to  be  in  perfect  health. 

Mr.  Graham  Brown  records  the  appearance  of  albu- 
men and  bile  pigments  in  the  urine  of  rabbits,  as  a  rare 
event,  after  bile  acid  salts  have  been  injected  under  the 
skin. J 

The  same  observer  noted  the  presence  of  red  blood 
corpuscles  once  or  twice  in  the  urine  ;  but  the  spectrum 
did  not  show  the  characteristic  absorption  bands  of 
blood  on  the  two  occasions  when  the  test  was  applied. 
This  is  another  instance  of  the  difference  in  the  effect 
caused,  according  as  the  poison  is  injected  into  the 
blood,  or  under  the  skin. 

Mr.  Graham  Brown  found  in  nearly  every  case  a 
great  rise  in  the  amount  of  nitrogen  excreted  by  the 

*  Frerichs,  Klinik  d.  Lcbcrkrankhciten,  Braunschweig,  1858,  Bd.  i.  p,  404.  See 
also  Arch.  f.  Anat.  u.  Phys,  1856,  p.  59,  note. 

f  Kiihne,  Arch.  f.  path.  Anat.  1858,  Bd.  xiv.  p.  324.  See  also  his  Lchrb.  d.  phys. 
Chemie,  Leipzig,  1866,  p.  8g. 

X  Graham  Brown,  Proceedings  of  the  Royal  Society  of  Edinburgh,  1875,  Vol.  viii. 
p.  528. 


and  their  Derivatives.  2ig 

urine  immediately  after  the  injection  of  the  bile  acid 
salts  under  the  skin  ;  in  one  case  the  amount  passed 
in  the  first  24  hours  after  the  injection  was  just  double 
the  average  of  the  three  foregoing  days. 

Feltz  and  Ritter  made  two  observations  with  the 
taurocholate  of  soda,  but  whether  it  were  injected  under 
the  skin  of  the  dog  or  into  the  veins  does  not  appear. 
They  noted  a  slight  increase  in  the  amount  of  nitrogen, 
but  it  was  so  slight  that  it  might  be  quite  within  the 
physiological  boundaries  ;  and  the  urea  was  markedly 
decreased  and  the  uric  acid  increased.*  The  urine 
seems  in  most  cases  to  be  alkaline. 

Physiological  Action   of    the    Derivatives   of   the 

Bile  Acids. 

Cholalic  acid.  It  was  noticed,  as  early  as  1854,  by 
Theodor  von  Dusch  that  cholalate  of  soda  dissolved 
the  red  corpuscles  as  readily  as  the  glycocholate,f  and 
Rohrig  found  that  the  pulse  became  more  rapidly  slow 
when  cholalate  of  soda  was  injected  into  the  veins, 
than  when  the  bile  acid  salts  themselves  were  used. J 

Hoppe-Seyler,  also,  saw  most  severe  symptoms 
follow  the  injection  of  two  grammes  of  the  same  salt 
into  the  jugular  vein  of  a  dog.  The  urine,  much 
decreased  in  quantity,  held  blood-colouring  matter  and 
albumen.  There  were  vomiting  and  diarrhoea,  and  in 
two  days  the  animal  was  dying.  After  death  many 
haemorrhages  were  found  in  the  intestines  which  held 
little  else  but  blood  and  bile.  The  kidneys  "on  section 
looked  quite  black  ;  and  the  tubules  were  filled  with 
blood  crystals. § 

*  Feltz  and  Ritter,  yotirnal  de  V Anatomic  et  de  la  Physiologie,  1874,  t.  x.  p.  5S5. 
f  Th.  von  Dusch,  Untersuchmgcn  und  Experimente  ah  Beitrag  zxir  Pathogcnese 
des  Ictcnis,  Leipzig,  1854,  p.  15. 

X  Rohrig,  Arch.  d.  Heilkunde,  1863,  p.  397. 

§  Hoppe-Seyler,  Arch.  f.  path.  Anat.  1862,  Bd.  xxv.  p.  183. 


220  Physiological  A  ction  of 

Feltz  and  Ritter  came  to  conclusions  quite  different 
from  those  of  observers  who  have  gone  before  them  ;  so 
different  that  it  would  almost  appear  that  they  experi- 
mented with  a  body  differing  in  chemical  composition. 
They  find  cholalate  of  soda  much  feebler  in  its  action 
than  the  glycocholate  and  the  taurocholate  ;  the  doses 
require  to  be  much  larger  to  produce  the  same  appear- 
ances. They  have  never  seen  any  blood  in  the  urine 
and  only  by  accident  any  colouring  matters.  The  blood 
also  does  not  appear  to  be  changed.* 

I  should  myself  feel  inclined  to  put  greater  trust  in 
the  observations  of  Rohrig  and  Hoppe-Seyler  on  the 
action  of  cholalic  acid,  than  in  those  of  Feltz  and  Ritter. 
For  it  would  be  a  strange  thing  if  a  body  which  is  the 
foundation  of  the  bile  acids,  and  allied  to  them  in  so 
many  chemical  and  physical  properties,  should  prove  as 
inert,  as  Feltz  and  Ritter  found  it,  in  its  physiological 
properties. 

Choloidic  Acid  (Demar9ay).  Feltz  and  Ritter  saw  no 
perceptible  changes  follow  the  injection  of  two  grammes 
of  the  soda  salt  of  this  acid  into  a  dog  weighing  5*750 
kilogrammesf 

Kiihne  states  that  the  red  corpuscle  is  dissolved  by 
choloidic  acid.  J 

Dyslysin.  This  body,  dissolved  in  cholalate  of  soda, 
was  injected  into  a  dog  by  Feltz  and  Ritter  in  doses 
of  two  grammes.  No  symptoms  whatever  were  no- 
ticed.§ 

GlycocoU.  All  observers  who  have  made  observations 
with  this  body  have  stated  that  it  is  harmless  to  the 
animal  ceconomy.H  Schultzen  and  Nencki  found  a 
great    increase    in    the    urea,     corresponding    to    the 

*  Feltz  and  Ritter,  Journal  dc  V Anatomic  ct  dc  la  Physiologic,  1875,  t.  xi.  p..  148. 

•j-  Feltz  and  Ritter,  loc.  cit. 

X  Kiiline,  Arch.  f.  path.  Anat.  1858,  Bd.  xiv.  p.  333. 

§  Feltz  and  Ritter,  loc.  cit. 

II  Rohrig,  op.  cit.  p.  396.     F-eltz  and  Ritter,  op.  cit.  p.  151. 


the  Bile  Pi/yments.  221 


"^5 


amount  of  nitrogen  in  the  glycocoll,  after  feeding 
animals  with  this  body ;  but  it  does  not  appear  to  have 
acted  in  any  way  as  a  poison.* 

Taimn.  Neither  is  taurin  endowed  with  any  very 
active  physiological  gifts.  Nearly  all  observers  look 
upon  it  as  inert.f  Salkowski,  however,  found  that 
rabbits  were  somewhat  sensitive  to  its  use,  much  more 
so  than  dogs  or  men.  When  given  by  the  mouth, 
the  greater  part  of  the  taurin  reappears  in  the  urine 
of  rabbits  ;  there  is  four  or  five  times  as  much  sul- 
phuric acid  as  natural  ;  and  it  is  to  the  waste  of 
alkali  that  Salkowski  attributes  the  injurious  action  of 
taurin. { 

Physiological  Action  of  the  Bile  Pigments. 

Rohrig  appears  to  have  been  the  first  to  make  experi- 
ments with  the  bile  pigments.  He  found  that  saturated 
solutions,  in  soap,  of  cholepyrrhin  (bilirubin)  and  of 
bilifulvin,  injected  into  the  circulation  in  doses  of 
6  to  8  C.C.  had  no  influence  on  the  action  of  the  heart.  § 

Feltz  and  Ritter  found  that  the  bile  pigments  had  no 
marked  action  on  the  animal  ceconomy.  The  injection 
of  bilirubin  was  followed  by  an  obstinate  constipation, 
and  an  increase  in  the  amount  of  urine  in  which  bilirubin 
could  be  readily  detected.  The  writers  note  much  the 
same  appearances  after  the  injection  of  biliprasin,  bilifus- 
cin,  and  bilihumin.^ 

To  sum  up,  it  may  be  stated  that  the  bile  pigments 
are  physiologically  inert. 

*  Schultzen  and  Nencki,  Zeitschriftf.  Biologie,  1872,  Bd.  viii,  p.  124. 

f  Th.  von  Dusch,  Rohrig,  and  Feltz  and  Ritter,  locis  citatis  ;  Koloman  Miiller, 
Arch.f.  cxp.  Pathologic,  1873,  Bd.  i.  p.  233; 

:j:  Salkowski,  Berichte  der  dcutschen  Chemischen  Gesellschaft  zu  Berlin,  1872. 
Jahrg.  V.  p.  637.  See  an  abstract  by  himself  of  his  work  in  Virchow  and  Hirsch's 
jfahrcsbcrichtf.  1873.     Bd.  i.  p.  159. 

§  Rohrig,  op.  cit.  p.  400.     Of.  p.  86.  of  this  work, 

%  Feltz  and  Ritter,  op.  cit.  p.  154. 


222  Dr.  Austin  Flint's  Views 

Physiological  Action  of  Cholestearin. 

Dr.  Austin  Flint,  the  younger,  first  called  attention 
in  1862*  and  again  in  a  pamphlet  published  in  the 
French  language  at  Paris  in  1868*}"  to  the  physiological 
action  of  cholestearin.  He  first  attempts  to  prove  that 
this  body  is  an  excremental  matter  formed  by  the 
metamorphosis  of  the  brain  and  excreted  by  the 
liver.  In  the  upper  part  of  the  intestine,  the  cho- 
lestearin is  changed  into  a  body  called  stercorin.  This 
is  then  cast  out  of  the  body  and  forms  a  most  im- 
portant element  in  the  excretions  of  the  body.  If  the 
liver  do  not  act  properly,  if  there  be  suppression  of  its 
secretion,  then  the  cholestearin  is  retained  in  the  blood 
and  acts  as  a  poison.  This  pathological  state  Dr. 
Flint  calls  cholestearsemia,  and  to  it  the  nervous  symp- 
toms seen  in  jaundice  may  be  set  down. 

It  may  be  noted  that  Dr.  Flint  made  no  direct  experi- 
ments with  cholestearin  upon  animals.  His  experiments 
are  a  series  of  estimations  of  the  amount  of  cholestearin 
in  the  blood.  The  trouble  and  uncertainty  which 
attend  all  estimations  of  bodies  in  the  blood  are  well 
known  ;  and  it  has  struck  me  in  looking  down  the  figures 
given  by  Dr.  Flint  that  in  very  many  cases  the  amount 
of  cholestearin  found  varies  inversely  with  the  amount 
of  blood  submitted  to  examination.  Where  a  larger 
amount  of  blood  has  been  examined,  a  smaller  per- 
centage of  cholestearin  has  been  found,  and  vice  versa. 

The  views  of  Dr.  Flint  have  not  met  with  universal 
acceptance ;  and  attempts  have  been  made  to  test 
their  value  by  directly  injecting  cholestearin  into  the 
blood.  A  difficulty,  however,  arises  from  the  insolu- 
bility of  cholestearin   in  the  ordinary  fluids   indifferent 

•  Austin  Flint,  jun.  American  yuuriial  of  the  Medical  Sciences,  1862.  vol.  xliv. 

P-  305- 

f  Recherches  exp.  suy  une  nouvelle  Fonciion  du  Foie,  Paris,  1868. 


on  the  Action  of  Cholestearin.  223 

to  the  blood.  Koloman  Miiller  made  a  sort  of  emul- 
sion by  first  finely  rubbing  up  the  cholestearin  with 
glycerine,  and  then  adding  solution  of  soap.  A  thick 
emulsion  was  thus  got  in  which  the  cholestearin  was 
very  finely  divided,  8.  C.C.  holding  45  milligrammes 
of  cholestearin.  This  emulsion  of  cholestearin  was  in- 
jected into  the  veins  of  about  g  dogs,  and  the  injection 
was  followed  by  coma,  and  death.  Koloman  Miiller 
concludes  that  the  nervous  appearances  seen  in  jaundice 
are  due  to  the  accumulation  of  cholestearin  in  the  blood.* 

It  would  be  worth  seeing  if  the  nervous  symptoms 
described  by  K.  Miiller  follow  an  injection  of  the  same 
emulsion  under  the  skin.  It  seems  very  likely  that  a 
thick  emulsion  injected  into  the  veins  would  be  fol- 
lowed by  severe  symptoms,  not  to  be  all  set  down  to 
the  physiological  action  of  cholestearin. 

On  the  other  side  are  the  experiments  of  several 
observers.  Pages,  the  year  after  Dr.  Austin  Flint 
published  his  pamphlet  in  French,  made  cholestearin 
the  subject  of  his  inaugural  thesis.  He  apparently  made 
his  experiments  under  the  direction  of  Feltz  and  Ritter. 
The  first  experiments  were  not  likely  to  give  any  in- 
formation, as  the  cholestearin  was  dissolved  in  aether, 
and  aether  is  a  fluid  to  which  the  "blood  is  by  no  means 
indifferent.  In  the  last  two  experiments  he  attempted 
to  dissolve  the  cholestearin  in  soap.  Koloman  Miiller 
says  that  he  was  unable  to  obtain  a  true  solution  with 
soap.  Be  this  as  it  may,  25  milligrammes  of  choles- 
tearin injected  into  the  veins  caused  no  symptoms 
whatever.  Pages  thinks  that  whatever  symptoms  are 
caused  by  cholestearin  are  due  to  its  solid  particles 
acting  as  emboli. f 


*  Koloman  Miiller,  Arch.f.  exp.  Pathologle,  1873,  Bd.  i.  p.  213. 

f  Henri  Pages,  De  la  cholcster'uie  et  de  son  accumulation  dans  Vccononiic,  These 
de  Strasbourg,  1869.  These  experiments  have  been  republished  by  Feltz  and 
Ritter,  Journal  de  V Anatomic  et  de  la  Physiologic,  1S75,  Annee  xi.  p.  166. 


224  Theory  of  Cholestearcemia 

A  Russian  observer,  M.  Chomjakow,  chose  oil  of 
almonds  as  a  vehicle.  A  5  per  cent,  solution  in  this 
oil  retained  its  transparency  at  37°  to  40°  C.  7*5 
C.C.  of  the  solution,  corresponding  to  345  milli- 
grammes of  cholestearin,  were  injected  into  the  veins 
of  cats.  The  following  were  the  results  :  either  the 
animals  underwent  the  injection  without  any  symptoms 
at  all,  or  death  followed  immediately  upon  the  injection 
either  of  cholestearin  in  solution  or  of  almond  oil  alone. 
In  this  case  the  cause  of  death  was  infarction  of  the 
pulmonary  artery.* 

V.  von  Krusenstern,  in  0.  Liebreich's  laboratory  at 
Berlin,  came  to  precisely  the  same  result  as  Chomjakow, 
but  with  a  different  solvent.  With  a  3  per  cent,  solution 
of  stearin  soap  he  made  a  0*5  per  cent,  solution  of  choles- 
tearin. The  daily  injection  of  this  solution  (10  to  go  C.C. 
=  5  to  45  milligrammes  of  cholestearin),  into  the  veins 
of  dogs  caused  not  the  least  change  in  their  state. f 

Looking  upon  these  experiments  and  comparing  them 
with  those  of  Koloman  Miiller,  it  will  be  hard  to  come  to 
any  other  conclusion  than  that  cholestearin  is  a  harm- 
less body,  the  injection  of  which  into  the  veins  is  fol- 
lowed by  no  evil  results.  If  this  position  be  granted, 
the  theory  of  a  cholestearaemia  must  fall. 

*  M.  Chomjakow,  Kriegsmedicinische  Zcitschrift   (Russian)  1872.      Quoted  by 
V.  von  Krusenstern,  Arch.  f.  path.  Anat.  1875,  Bd.  Ixv.  p.  412. 
f  v.  von  Krusenstern,  op.  cit.  p.  418. 


CHAPTER   X. 

The  Etymology,  History,  and  ^Etiology  of  Jaundice. 

Jaundice  signifies  a  yellowness  of  the  skin.  It  comes 
from  the  French  word  jaune,  yellow.  The  Greeks 
called  the  disease  icterus.  Of  this  word  Aretseus  says  : 
"it  is  derived  from  certain  four-footed  and  terrestrial 
animals,  called  hrih$  whose  eyes  are  of  this  colour."* 
Pliny  the  elder,  on  the  other  hand,  says  there  is  a  bird 
called  icterus,  the  sight  of  which  was  cure  to  the  jaun- 
diced patient,  but  death  to  the  bird.f  Aretaeus  is,  no 
doubt,  right.  The  disease  must  have  had  a  name 
before  a  means  for  its  cure  was  described  :  and  the 
Greeks  were  in  the  habit  of  keeping  these  ^ktiSss  for  the 
same  purpose  as  we  do  cats,$  so  that  the  source  of 
comparison  would  be  at  hand. 

Suidas  derives  the  word  icterus  from  IjirTvo?,  a  kite  :§ 
because,  says  de  Haen,l|  they  also  have  jaundiced  eyes. 

The  Latins  called  jaundice  morbus  regius,  from  the 
yellow  colour  of  gold,  the  Rex  metallontm,  and  not  from 
the   royal    diet  or  regimen  which  was  believed   to  be 

*  Aretaeus,  On  the  Causes  and  Symptoms  of  Chronic  Diseases,  Bk.  i.  chap.  xv. 
Adams'  trans.  Syd.  Soc.  1856,  p.  326. 

f  C.  Plinii  Sec.  Nat.  Hist.  Lib.  xxx.  Cap.  xi.  Lugd.  Bat,  1669,  t.  iii.  p.  321. 
This  bird  was  called  galbiila  ox  galgtila  by  the  Romans,  and  is  supposed  to  have 
been  the  golden  oriole. 

+  Dr.  Rolleston  {Journal  of  Anat.  and  Phys.  1868,  Vol.  ii.  p.  47)  is  of  opinion  that 
the  "aris  performed  the  same  office  in  Greek  houses  as  the  felis  doinestica  in 
ours,  viz.  that  of  killing  mice.  The  'Uns  appears  to  be  the  yellow-breasted  marten; 
and  not  a  ferret,  as  some  writers  state. 

§  Suidas,  Lexicon,  t.  ii.  ed,  Kuster.  Cantabrig.  1705. 

II  De  Haen,  Prcelectiones,  Vienna,  1780,  t.  ii.  Tract,  dc  verniibus,  etc.  p.  108. 
Villeneuve  gives  also  another  derivation :  "  quelques-uns  font  deriver  la  denomi- 
nation dont  il  s'agit  d'  "ktis,  lar'/n'So;,  (sic)  espece  de  mouches  de  bois  dont  les  yeux 
sent  de  couleur  jaune."     {Diet.  d.  Sci.  incd.  Paris,  1S18,  t.  xxiii.  p.  386.) 

Q 


226  Derivation  of  Jaimdice. 

good  for  the  patient.*  For  the  same  reason,  another 
Latin  synonym  is  aunigo^  or  aurigo  from  aurum^  gold. 
Also  morbus  arciiatus^  seu  arqitatus,  from  the  circles  seen 
by  the  jaundiced. f 

By  the  Germans,  jaundice  is  called  Gelbsucht,  although 
of  late  years  the  growing  custom  of  using  words  of  a 
non-Teutonic  source  has  made  this  excellent  name  give 
way  almost  entirely  to  icterus.  By  the  French,  jaimisse 
is  almost  forgotten,  or  thought  vulgar,  and  ictere  is 
always  used. 

Jaundice  could  hardly  fail  to  be  noticed  early  in  the 
history  of  mankind,  as  the  x:hange  of  complexion  and 
colour  would  be  a  striking  appearance.  Accordingly 
there  is  abundant  mention  of  it  in  the  genuine  Hippo- 
cratic  writings,  which  most  often  speak  of  it  as  a 
complication  of  other  diseases,  chiefly  fevers.  In  the 
Aphorisms  it  is  said  to  be  a  bad  sign  if  the  liver  become 
hard  during  a  jaundice  ;  and  in  the  third  book  of  the 
Epidemics,  that  an  habitual  pain  in  the  neighbourhood  of 
the  liver,  with  other  symptoms,  preceded  a  jaundice. J 
It  may  be  disputed  if  the  father  of  medicine  conceived 

*  Celsus,  Medicin.  Lib.  iii.  cap.  xxiv.  "  Per  omne  vero  tempus  utendum  est 
exercitatione,  frictione  :  si  hiems  est,  balneo;  si  aestas,  frigidis  natationibus  ;  lecto 
etiam  et  conclavi  cultiore,  lusu,  joco,  ludis,  lascivia  per  quas  mens  exhilaretur :  ob 
quae  regius  morbus  dictus  videtur."  Others  may  think  that  as  mental  worry  pre- 
disposes to  jaundice,  so  it  is  called  the  royal  disease  from  the  anxieties  of  court 
life.  It  is  not  every  one  who  can  have  the  stoical  virtue  of  Antoninus  and  say: 
"  Even  in  a  palace,  life  may  be  led  well." 

I  have  been  told  the  very  place  transforms  men. 

And  that  not  one  of  a  thousand,  that  before 

Lived  honestly  in  the  country  on  plain  salads, 

But  bring  him  thither,  mark  me  that,  and  feed  him 

But  a  month  or  two  with  custards  and  court  cake-bread, 

And  he  turns  knave  immediately.     I'd  be  honest; 

But  I  must  follow  the  fashion,  or  die  a  beggar. 

Massinger  :  Great  Duke  of  Florence,  I.  i. 
f  Paracelsus  is  said  to  have  called  jaundice  morbus  hiscoli  from  the  salt  which 
he  administered  in  these  cases ;  but  in  his  writings  he  seems  to  me  to  have  very 
frequently  used  the  word  icterus  or  ictcritia. 

t  Hippocrates,  Aphorism.  Sect.  vi.  §  42,  and  Epidcm.  lib.  iii.  13th  patient,  case 
of  Apollonius  of  Abdera.     Littre's  ed.  t.  iv.  p.  574,  and  t.  iii.  p.  138. 


Early  History  of  Jaundice.  227 

any  relation  between  the  bile  secreted  by  the  liver  and 
the  symptom  of  jaundice.  In  the  other  books  of  the 
Hippocratic  Collection  it  is  said  that  the  deep  yellow 
colour  and  the  white  colour  come  from  the  liver  or 
disease  of  the  liver :  and  in  these  states,  the  jaundices, 
dropsies,  and  leucophlegmasise  which  come  from  the 
liver  are  whitish,  while  those  from  the  spleen  are  more 
dark.*  Another  white  jaundice  is  spoken  of  as  coming 
from  phlegm,  and  attacking  chiefly  in  the  winter.  Its 
colour  is  white,  and  the  chest  is  filled  with  phlegm.  The 
urine  is  white  and  thick.f  This  certainly  does  not 
correspond  to  what  we  call  jaundice,  nor  does  the 
second  kind  of  jaundice  described  just  before  by  the 
same  writer.  The  first  and  the  third  are  more  like  the 
symptom  as  we  speak  of  it  to-day.  The  first  kind  is 
caused  by  the  bile  being  put  in  movement,  and  being  fixed 
in  the  skin  and  head,  J  so  that  the  body  is  as  yellow  as  a 
pomegranate.  The  eyes  are  yellow,  the  stools  white 
and  stinking.  It  will  be  seen  that  some  caution  must 
be  used  when  early  writers  speak  of  'Urspog  for  they  do 
not  always  mean  the  same  as  we  do  ;  and  like  confu- 
sion has  been  seen  almost  in  our  own  day. 

Galen  also  asserts  that  the  yellow  bile,  when  it  is 
carried  all  over  the  body,  still  keeping  its  own  nature, 
causes  a  disease  called  jaundice. §  Aretseus  says  much 
the  same  thing,  adding,  however,  that  jaundice  may  arise 
from  the  stomach,  spleen,  kidneys,  and  colon,  and  is  not 
solely  formed  from  the  liver  as  some  have  supposed. I| 
The  jaundice  caused  by  the  liver  is  brought  about  in 
this  fashion  :  if  the  liver  and  gall  bladder  continue   to 


*  Epidem.  Lib.  ii.  Sect.  i.  Cap.  x.  Littre's  ed.  t.  v.  p.  83. 

t  De  aff.  int.  Cap.  xxxviii.  Littre's  ed.  t.  vii.  p.  261. 

X  The  same  view  of  the  pathology  of  the  disease  is  taken  by  the  writer  de  affect. 
(Cap.  xxxii.  Littre's  ed.  t.  vi.  p.  245.) 

§  Galen,  De  vied,  method.  Lib.  ii.  Cap.  i.  Kiihn's  ed.  Lips.  1826,  Vol.   xi.   p.  74. 

II  Aret£eus,  On  the  Causes  and  Symptoms  of  Chronic  Diseases,  Bk.  i.  Chapter  xv. 
Adams'  translation,  p.  324. 

Q2 


228  Early  History  of  Jaundice. 

secrete  bile,  but  the  passages  which  convey  the  bile  to 
the  intestine  be  obstructed,  the  bile  regurgitates ;  it 
therefore  becomes  mixed  with  the  blood,  and  the  blood 
passing  over  the  whole  system  carries  the  bile  into 
every  part  of  the  body,  which  acquires  the  appearance 
of  bile.  It  would  be  hard  to  express  in  different  lan- 
guage the  doctrine  of  jaundice  from  absorption,  now 
universally  held. 

Aetius  gives  the  views  of  Galen  and  Ruffus  ;  he  says : 
Jaundice  is  an  effusion  of  bile  all  over  the  body.  They 
err  who  think  that  in  all  cases  of  jaundice  the  liver  must 
be  diseased.  Sometimes  a  jaundice  is  caused  by  weak- 
ness of  the  gall  bladder,  which  does  not  draw  to  itself 
the  bile  out  of  the  liver,  as  it  accustomed,  and  thus 
leaves  the  blood  impure.*  Paul  teaches  that  jaundice 
is  a  diffusion  of  the  bile  all  over  the  body,  sometimes 
of  the  yellow,  sometimes  of  the  black,  bile.  Jaundice 
with  fever  would  seem  to  be  caused  by  a  hot  inflamma- 
tion of  the  liver  which  renders  the  blood  bilious.  A  jaun- 
dice without  fever  is  caused  by  an  affection  of  the  gall 
bladder  and  its  ducts. t 

With  Paul  the  list  of  the  Greek  and  Latin  writers 
ends,  and  the  Arabians,  to  whom  medicine  and  civilisa- 
tion are  so  much  indebted,  give  us  a  physiology  but 
little  different  from  that  of  the  classical  writers. 

Amongst  the  dreams  of  Paracelsus  will  be  found  the 
statement,  apparently  as  a  reaction  against  the  humoral 
pathology,  that  the  bile  never  causes  any  disease. 
Jaundice  is  not  due  to  the  bile  but  to  the  union  of 
three  salts,  "  sa/  entalicum,  sal  vitriolatum,  et  liquor  sul- 
phuris  resoluti.^^X 

*  Aetius,  Tetrahibl.  III.  serm.  ii.  cap.  xvii.  Basil.  1542,  p.  582. 

f  Paul  of  iEgina,  Book  iii.  Cap.  L.  Adams'  trans.  Vol.  i.  p.  580.  See  p.  582  for 
a  general  view  of  the  classical  writers. 

+  Paracelsus,  Opera,  Genevae,  1658,  Vol.  i.  p.  486.  De  Icteritiis.  It  would  seem 
very  doubtful,  more  so  than  in  the  case  of  the  classical  writers,  what  Paracelsus 
meant  by  icteritia.     He  indeed  begins  this  book  witli  :    "  Icterus  sive  icteritia," 


Hcematogenous  Jaundice.  229 

Sylvius  de  le  Boe  denies  that  obstruction  in  the  bile 
ducts  is  an  efficient  cause  of  jaundice.*  He  points  out 
that  in  some  cases  of  jaundice,  which  he  has  dissected, 
he  had  found  no  obstruction  ;  and  further,  that  in  some 
cases  the  stools  were  coloured,  or  but  little  less  coloured 
than  usual.  With  this  writer,  an  important  age,  not 
merely  in  the  history  of  jaundice,  but  in  that  of 
medicine  at  large,  is  reached.  It  is  the  time  of  the 
discovery  of  the  circulation  by  Harvey,  of  the  lacteals 
by  Aselli,  and  of  the  thoracic  duct  by  Pecquet.  With 
the  changes  in  physiology,  changes  in  pathology  like- 
wise appear.  The  history  of  jaundice  must  now  be 
broken  up  into  three  heads  :  i.  a  theory  which  attri- 
butes the  symptom  of  jaundice  to  changes  in  the  blood 
and  its  colouring  matter,  thence  called  hsematogenous 
jaundice :  ii.  a  theory  which  makes  the  bile  to  be 
merely  separated  by  the  liver  from  existing  elements 
in  the  blood,  not  truly  secreted  by  the  liver  ;  jaundice 
may  thus  arise  when  the  liver  ceases  to  excrete  the  bile, 
the  elements  of  which  accumulate  in  the  blood  and 
cause  the  general  yellow  appearance :  iii.  a  theory 
which  attributes  the  phsenomena  of  jaundice  to  the 
absorption  into  the  mass  of  the  blood  of  bile  already 
formed.  Under  these  three  heads  all  prevailing  doc- 
trines of  jaundice  may  be  discussed. 

I.  The  notion  of  a  hsematogenous  jaundice  is  cer- 
tainly to  be  found  in  Aretaeus,  He  speaks  of  divers 
causes  of  jaundice,  not  only  from  the  liver,  but  from  the 
stomach,  the  spleen,  the  kidneys,  and  the  colon.  But, 
besides  jaundice  from  the  viscera,  "the  general  system 
is  most  powerful  in  producing  icterus;"  and  "if  indi- 
gestion happen   in  the  blood,  the  blood    assumes   the 

but  he  goes  on  to  speak  of  icteritia  of  the  brain,  kidneys,  and  spleen  ;  of  local 
icteritia  of  the  limbs,  and  of  red,  white,  and  black  icteritia.  Red  icteritia  seems 
to  be  erysipelas. 

♦  Sylvius  de  le  Boe,  Praxeos  med.  Lib.  i.  cap.  xlvi.  Opera  viedica,  Amstelodami, 
1679,  p.  301. 


230  H cEmatogenons  Jaundice. 

appearance  of  bile,  but  is  distributed  as  nourishment  to 
all  parts,  wherefore  bile  appears  everywhere."*  Galen 
likewise  discusses  the  question  if  jaundice  may  be  seen 
without  disorder  of  the  liver.  He  says  he  has  seen, 
without  any  disease  of  this  organ,  a  critical  effusion  of 
bile  on  the  skin,  and  also  that  he  had  seen  a  change  of 
blood  into  bilef  from  some  strange  corruption  such 
as  follows  the  bites  of  beasts,  and  for  this  he  instances 
a  case  of  jaundice  following  snake  bite.  This  may  be 
due  to  some  change  in  the  humours  wrought  by  the 
poison.  These  ideas  do  not  seem  to  have  taken  much 
root  among  physicians,  for  there  seems  to  be  no  men- 
tionj  of  the  theory  of  hsematogenous  jaundice  until 
Bianchi  again  distinctly  enunciated  it.§  This  writer 
speaks  of  two  kinds  of  jaundice,  one  caused  by  disease 
of  the  liver,  the  other  by  a  solution  of  the  blood,  in  which 
the  motions  do  not  become  white,  but  are  rather  more 
deeply  coloured.  It  is  more  quickly  brought  about  than 
the  other  kind  of  jaundice,  and  is  seen  in  fevers  and  after 
the  bites  of  vipers.  This  view  is  shared  by  certain  ob- 
scure writers  upon  jaundice  and  bilious  diseases. ||  It  was 
upheld  for  a  time  by  Reil,  who,  under  the  name  of  poly- 
cholia,  gave  a  long  description  of  what  is  now  called 
haematogenous  jaundice,  with  rules  for  distinguishing  it 

•  Aretaeus,  op.  cit.  p.  326.  Leo,  likewise,  says  that  jaundice  may  arise  from  the 
conversion  of  blood  into  bile  from  heat  of  the  system.  (Quoted  by  Adams  in  his 
translation  of  Paulus  ^ginetus,  vol.  i.  p.  585.) 

■f-  o^aroLi  Ss  Kcu  ^oi^);  K^iffiois  ix.p(^oXov/u,ivo\i  iviort  to  aifjio,.  Galen,  de  loc.  ajf.  Lib.  V. 
cap.  viii.  ed.  Kiihn,  Lipsiae,  1824,  vol.  viii.  p.  355. 

\  I  have  been  unable  to  find  any  trace  of  this  doctrine  in  the  writings  of  Sydenham. 
One  passage  (Ohs.  med.  iv.  3,  §  8,  Opera  ovinia,  ed.  Greenhill,  p.  170.)  is  thought 
by  Eisenmann  to  have  a  faint  likeness  to  this  teaching.  To  me  it  seems  merely 
the  explanation  of  a  kind  of  dysentery  by  invoking  a  disease  of  the  blood,  the  hot 
and  acrid  humours  of  which  are  thrown  upon  the  gut  by  the  mesenteric  arteries. 
Nor  can  I  find  anything  in  Baillou's  chapter  on  the  epidemics  of  1575,  which 
would  remind  the  reader  of  the  theory.  {Epidhnies  et  iplieincridcs,  ed.  Yvaren, 
Paris,  1858,  p.  278.) 

§  Bianchi,  Historia  Hcpatica,  Genevae,  1725,  3tia  ed.  t.  i.  pars  ii.  cap.  x.  p.  185, 

II  For  the  bibliography  of  bilious  fevers,  see  Eisenmann's  Die  Krankheits-Familie 
Cholosis,  Erlangen,  1836. 


and  its  early  Supporters.  231 

from  true  jaundice.*  The  opinion  was  resisted  by 
Cullen,  who  says  that  jaundice  must  be  the  result  of 
bile,  once  secreted,  being  taken  up  into  the  blood-ves- 
sels ;t  by  Donald  Monro, J  Eller,§  and  Selle  ;||  they  all 
teach  that  the  doctrine  of  jaundice  from  absorption  is 
the  only  trustworthy  theory. 

No  further  important  support  is  met  with  until  the 
time  of  Saunders,  who  speaks  of  the  experiments  of 
Fourcroy  and  VauqueHn.^  These  observers  made  a 
sort  of  artificial  bile  by  heating  together  ox  blood  and 
water.  Saunders  then  adds:  "  it  would  appear  prob- 
able, that,  under  certain  morbid  states  of  the  body,  the 
blood  may  acquire  a  bilious  appearance,  independent 
of  absorption  or  regurgitation  from  the  liver."**  It  is 
worthy  of  note  that  the  man,  who  was  the  first  to  prove 
by  experiment  the  doctrine  of  jaundice  from  absorption, 
should  likewise  have  given  the  weight  of  his  authority  to 
the  theory  of  a  hsematogenous  jaundice. 

One  of  the  next  notices  of  a  jaundice  arising  from 
changes  in  the  blood,  without  any  implication  of  the  liver, 
may  be  found  in  the  writings  of  Breschet.  After  pointing 
out  the  near  relation  which  exists  between  melanosis 
and  the  colouring  matter  of  the  blood,  he  says  that  he 
presumes  that  jaundice  is  brought  about  much  less  by 
the  bile  than  by  the  blood, ft  and  he  attributes  the  jaun- 


*  Reil,  Tractatus  de  Polycholia,  Halae,  1782,  p.  47.  He  withdrew  the  opinions 
expressed  in  this  "juvenile  opus,"  as  he  calls  it,  a  few  years  later,  and  says  that  no 
bile,  nor  anything  like  bile  is  made,  save  by  the  help  of  the  liver.  {Memorabil. 
Clinic,  fasc.  iv.  Halae,  1795,  p.  48.) 

f  Cullen,  First  Lines  of  the  Practice  of  Physic,  §   1817. 

X  Donald  Monro,  An  Accoiint  of  the  Diseases  which  were  most  frequent  in  the 
British  Military  Hospitals  in  Germany,  London,  1764,  p.  206. 

§  Eller,  Obs.  de  cog.  et  cur.  morb.  Venetiis,  1767,  Sect.  ix.  p.  177. 

II  Selle,  De  curand.  horn.  morb.  Berolini,  1798,  ed.  Sprengel,  p.  184. 

IT  Fourcroy  and  Vauquelin,  Annates  de  Chemie,  1790,  t.  vi.  p.  181. 

**  Saunders,  A  Treatise  on  the  Structure,  Economy,  a)id  Diseases  of  the  Liver, 
London,  1803,  3rd  edition,  p.  105,  note. 

f  f  Breschet,  Considerations  sur  iine  alteration  organiqne  appelcc  degencresccnce 
noire,  etc.  Paris,  1821,  p.  21.     Andral  {Clinique  med,  Paris,  1839,  t.  ii.  p.  287.) 


232  Discussion  of  the  Theory 

dice  so  common  in  the  new  born  to  changes  in  the  cir- 
culation rather  than  in  the  hver,*  Later  on  Virchow 
contributed  much  to  the  spread  of  this  notion  of  an  icterus 
paradoxus.  He  made  known  the  hkeness  between  hsema- 
toidin  and  bile  pigment,  both  in  crystallization  and  chemi- 
cal reaction. f  The  identity  of  these  two  substances  was 
thought  to  have  been  proved  by  Zenker  and  Funke,J 
Valentiner,§  and  later  still  by  Ja£fe.||  But  Stadeler^f 
and  Holm**  deny  this  and  give  rules  by  means  of  which 
hsematoidin  may  be  distinguished  from  bilirubin.  Sal- 
kowski  on  the  other  hand,  says  that  a  substance,  with 
many  of  the  characters  of  haematoidin,  which  he  found 
in  the  thyroid  gland,  and  which  must  therefore  have  its 
origin  in  the  blood,  was  insoluble  in  cether,  and  soluble 
in  alkalies,  which  Holm  and  Stadeler  assert  to  be  cha- 
racteristic of  bilirubin. tt  Thudichum,  however,  would 
affirm  that  the  body  which  all  these  observers  analysed 
was  neither  bilirubin  nor  hsematoidin  but  luteinJJ  the 
hsemolutein  of  Piccolo  and  Lieben.§§  Thudichum 
further  protests  against  the  idea  of  the  bile  pigments 
being  derived  from  hsematoidin  because  they  contain 
no  iron. II II     There  is,  however,  a  hsematin  free  from  iron 

would  seem,  with  Breschet,  to  favour  the  notion  that  the  colour  in  the  newly  born, 
or  in  yellow  fever,  is  due  to  changes  in  the  circulation  or  to  a  sort  of  general  ecchy- 
mosis.     The  same  thought  is  before  expressed,    (t.  i.  p.  6oi.) 

*  In  the  old  Chinese  system  of  physiology,  the  reverse  was  believed  ;  the  liver 
was  the  source  of  all  the  pigments  in  the  body. 

t  Virchow,  Arch.  f.  path.  Anat.  Bd.  i.  1847,  P-  37°'  See  also  Ges.  Abh.  Hamm, 
1862,  p.  849. 

%  Funke,  Lchrh.  d.  Phys.  Leipzig,  i860,  Bd.  i.  p.  246. 

§  Valentiner,  quoted  by  Steiner,  Arch  f.  Anat.  u.  Phys.  1873,  p.  163. 

II  Jaffe,  Arch./,  path.  Anat.  1862,  Bd.  xxiii.  p.  192.  He  obtained  bilirubin  from 
an  old  haemorrhage  into  the  brain. 

H  Stadeler,  Annul,  d.  Chcmie  und  Pharm.  1864,  Bd.  cxxxii.  p.  343. 

**  Holm,  yournalf.prakt.  Chemic,  1867,  Bd.  c.  p.  142. 

ff  Salkowski,  Mcd.-Chcm.  Untcrsuch.  Hrsg.  von  Hoppe-Seyler,  1868,  Heft.  iii. 
p.  436.  Hoppe-Seyler  found  bilirubin  in  a  cyst  of  the  breast.  [Arch.  f.  path.  Anat. 
1862,  Bd.  xxiv.  p.  10.) 

\X  Thudichum,  Proc.  of  the  Royal  Society  of  London,  1869,  Vol.  xvii.  p.  255. 

§§  Piccolo  and  Lieben,  Giornalc  di  scicnze naturali cd  cconoinichc,  Palermo,  1866, 
Vol.  ii.  p.  258. 

II  jl  Thudichum,  Zcitschrift  f.  rat.  Med.  Bericht  f.  1868,  p.  223. 


of  H cematogenous  Jatmdice.  233 

which  Is  asserted  to  be  polymeric  with  bilirubin  ;  yet 
it  seems  strange  that  haemoglobin  should  so  readily 
part  with  its  iron.  Dr.  Young  found  in  some  careful 
experiments  under  Prof.  Gamgee's  direction  that  the 
ash  of  the  bile  was  rich  in  iron,*  and  this  fact  is  also 
worthy  of  being  kept  in  mind.f 

Preyer  seems  decidedly  of  opinion  that  hsematoidin 
and  bilirubin  are  not  the  same  bodies.  He  finds  that 
the  spectra  of  the  two  are  altogether  different ;  the 
colouring  power  of  hsematoidin  is  also  much  weaker 
than  that  of  bilirubin.:!:  It  certainly  does  seem  that  no 
satisfactory  elementary  analysis  of  hasmatoidin  has  yet 
been  made  ;  in  Robin's  case  it  is  doubtful  if  he  had  to 
do  with  haematoidin  at  all.  With  this  exception,  hae- 
matoidin  has  been  examined  in  but  very  minute  quan- 
tities, only  to  be  recognised  with  the  microscope.  If 
the  spectra  be  so  entirely  different,  it  will  be  hard 
hereafter  to  maintain  the  identity  of  the  two  bodies, 
even  if  the  elementary  analysis  prove  to  be  very  similar. 
Mr.  Sorby,  however,  seems  to  think  that  the  spectra  of 
bile  from  snails  and  of  haematin  are  closely  akin.§  It 
will  be  necessary,  however,  to  extend  this  observation  to 
vertebrates,  before  any  result  valuable  to  the  physician 
can  be  obtained.  Maly  also  found  that  the  crystals  of 
bilirubin  showed  under  the  microscope  a  convex  appear- 
ance, like  that  of  the  section  of  a  biconvex  lens.  ||      The 

*  p.  A.  Young,  jfo2irnal  of  Anatomy  and  Physiology,  Vol.  v.  1871,  p.  158. 
Robin  (Comptes  rendus,  1855,  t.  xli.  p.  506)  found  iron  in  the  ash  of  the  red  matter 
found  in  echinococci  cysts  in  the  liver ;  about  -0002  per  cent.  Robin  calls  this 
red  matter  hsmatoidin,  but  I  venture  to  express  a  doubt  as  to  the  propriety  of  so 
naming  it.  The  source  is  highly  suspicious,  and  it  is  known  how  very  often 
hydatid  cysts  communicate  with  the  gall  ducts.  The  percentage  analysis  agrees 
tolerably  closely  with  that  of  bilirubin. 

t  See  also  the  discussion  of  the  relation  between  bilirubin  and  hasmatoidin  at  p. 
32  of  this  work, 

X  W.  Preyer,  Die  Blutkrystalle,  Jena,  1871,  p.  187. 

§  Sorby,  Quarterly  Journal  of  Microscopical  Science,  1876,  Vol.  xvi.  p.  78. 

II  Maly,  Sitznngsberichte  der  math.-naticrw.  Classe  d.  kaiserlichen  Akademie, 
Wien,  1868,  Bd.  Ivii.  Abth.  ii,  p.  97. 


234  Discussion  of  the  Theory 

crystals  of  haematoidin  have  always  a  rhomboidal  ap- 
pearance. 

The  notion  of  the  identity  of  bilirubin  and  haema- 
toidin being  once  set  up  in  the  minds  of  physiological 
chemists,  it  seemed  no  strange  statement  that  the  bile 
pigments  should  appear  in  the  urine  when  any' large 
number  of  the  blood  corpuscles  were  dissolved.  This 
indeed  is  what  Frerichs  found  after  the  injection  of  the 
bile  acids  into  the  blood,  a  fact  explained  by  him  in 
altogether  another  way.*  Kiihne,  likewise  upheld 
Frerichs'  belief,  and  added  a  new  fact,  that  the  bile 
pigments  appear  in  the  urine  after  the  injection  of 
haemoglobin  into  the  circulation. •]*  M.  Herrmann  also 
found  these  after  the  injection  of  large  quantities  of 
water  into  the  veins  ]%  Nothnagel,  after  the  injection 
of  aether  and  chloroform  ;§  Munk  and  Leyden,  after  the 
injection  of  phosphoric  acid  :|i  all  these  bodies  having 
the  power  of  dissolving  the  red  blood-corpuscles  and 
thus  setting  the  haemoglobin  free  in  the  blood-vessels. 

The  theory  of  hsematogenous  jaundice  seemed  thus 
to  receive  great  support  from  experiment. 

But  it  was  assumed  with  too  great  haste  that  if  the 
colouring  matter  of  the  bile  were  present  in  the  urine, 
that  jaundice  was  thus  of  necessity  at  hand.  It  is 
indeed  true  that  the  urine  is  often  the  first  to  give 
notice  of  a  coming  attack  of  jaundice,  even  before  the 
conjunctiva  ;  but  it  is  well  to  point  out  with  Virchow^ 

*  Frerichs,  Klinik  d.  Leberkrankheiten,  Braunschweig,  1858,  Bd.  i.  p.  405.  See 
also  Arch.f.  Anat.  u.  Phys.  1856,  p.  59,  note. 

t  Kiihne,  Arch.  f.  path.  Anat.  1858,  Bd.  xiv.  p.  337.  See  also  Lchrh.  d.  phys. 
Cheniie,  Leipzig,  1866,  p.  89. 

J  M.  Herrmann,  Dc  effectu  sanguinis  dilnti  in  sccrctioncni  tcrlncs,  Diss.  Inaug. 
Berolin.  1859,  p.  23. 

§  Nothnagel,  Berliner  klin.  Wochenschr.  1866,  p.  31. 

II  Munk  and  Lej'den,  Die  acute  Phosphorvergiftung,  Berlin,  1865,  p.  129. 

IT  Virchow,  Arch.  f.  path.  Anat.  1865,  Bd.  xxxii.  p.  120,  Poncet  has  at- 
tempted to  cause  jaundice  by  the  injection  of  blood  under  the  skin  of  animals  ;  he 
found  a  high-coloured  urine  was  passed,  but  strange  to  say,  no  chemical  tests 
were  used,     {de  Victcre  hematique  trauinatique,  These  de  Paris,  1874,  p.  61.) 


of  HcBinatogenous  Jaundice.  235 

that  in  non^  of  these  experiments  has  a  real  jaundice 
been  brought  about.  There  has  never  been  a  yellow 
staining  of  the  tissues,  but  only  a  reaction  of  bile  pig- 
ment in  the  urine  ;  and  between  these  two  states  there 
is  a  deep  and  wide  division.  No  artificial  jaundice  has 
been  as  yet  caused  by  injecting  any  quantity  of  bile 
into  the  blood,*  though  it  would  seem  possible  that 
jaundice  mighf  follow,  if  substances  which  destroy  the 
blood-corpuscles  were  allowed  slowly  to  act  upon  the 
oeconomy. 

The  likelihood  of  this  last  observation  of  Virchow's 
to  be  true  has  of  late  years  somewhat  decreased.  The 
foregoing  experiments  upon  which  so  much  stress  has 
been  laid  have  been  repeated,  and  in  general,  no  bile 
pigment  has  been  detected  in  the  urine  after  the  injec- 
tion of  substances  which  dissolve  the  blood-corpuscles. 
Naunyn  was  the  first  to  repeat  these  observations!  and 
he  could  not  succeed  in  obtaining  a  reaction  peculiar 
to  the  bile  pigment  after  the  injection  of  hsemoglobin 
into  the  circulation  or  under  the  skin.  In  both  cases  the 
urine  might  contain  blood  colouring  matter,  but  no  bile 
pigment.  J.  Steiner,  likewise,  repeated  M.  Herrmann's 
observations,  and  found  that  no  bile  pigment  was  pre- 
sent in  the  urine  after  the  injection  of  large  quantities  of 
water.J  I  myself  have  been  unable  to  detect  the  pre- 
sence of  bile  pigment  in  the  urine   after  the   injection 

*  Dr.  George  Harley  indeed  states  that  he  has  succeeded  in  making  a  dog 
jaundiced  by  injecting  the  bile  of  other  dogs  under  the  skin.  He  failed,  however, 
in  two  other  experiments,  {jaundice  :  its  pathology  and  treatment,  London,  1863, 
p.  96.) 

f  Naunyn,  Arch.f.  Anat.  andPhys.  1868,  p.  410. 

l>ia.sseXSitzungsberichte  d.  Marburg.  Gesellschaft,  1875,  No.  2.  quoted  in  Hayem's 
Revue  des  Sciences  med.  1876,  t.  vii.  p.  530)  found  that  the  urine  gave  no  reaction 
with  nitric  acid  after  the  injection  of  large  quantities  of  blood  into  the  stomach 
of  dogs;  but  (Hofmannand  Schwsdhe's  jfahresb.  d.  Anat.  ri.Phys.  f.  1874,  iii.  Abth. 
p.  182.)  the  same  observer  is  reported  to  have  found  that  after  injecting  a  great 
quantity  of  dissolved  corpuscles  into  the  stomach  of  one  dog,  the  urine  shows  traces 
of  bile  pigment  on  the  second  and  third  day,  not  the  first. 

X  J.  Steiner,  ibid.  1873,  p.  160. 


236  Discussion  of  the  Theory 

into  the  circulation  of  the  bile  acids,  notwithstanding 
the  statements  to  the  contrary  of  Frerichs  and  Kiihne. 
Furthermore,  Naunyn,  after  the  injection  of  aether  under 
the  skin  found  well-marked  signs  of  the  presence  of  hae- 
moglobin in  the  urine  in  all  cases  ;  but  in  only  one  out 
of  four  could  a  certain  opinion  be  given  as  to  the  pre- 
sence of  bile  pigment.* 

This    great    difference    between    observers    so   trust- 
worthy  may,    I  think,  best   be   explained   by  the   fact 
that  Frerichs,  Kuehne  and  Herrmann  seemed  to  have 
used  for  their  experiments  dogs,  in  whose  urine   a  sub- 
stance which  gives  all  the  reactions  of  bile  pigment  is 
an  almost  constant  constituent. f     Naunyn,  Steiner  and 
myself  have  used  rabbits  exclusively  for  experiment,  and 
in  the  urine  of  these  animals,  unless  fasting,  bile  pig- 
ment is  not  often  seen.     These  later  experiments  would 
therefore  seem  more  trustworthy  than  those  of  Kiihne 
and  Frerichs,  and  I  do  not  think  that  their  value   has 
been  destroyed  by  Tarchanoff's  recent  observations,  for 
although  after  the  injection  of  haemoglobin  into  the  cir- 
culation bile  pigment  was  seen  in   the  urine,  yet  the 
experiments  themselves  are  not  such   as  to  command 
confidence.     In  the  first  place,  dogs  were  used,  in  some 
cases  even  without  testing  the  urine  beforehand  for  bile 
pigment ;    and  further  it  was  not  expressly  stated  that 
the  animal  was  not  fasting,  and  most  of  the  experiments 
lasted  over  six  hours,  at  the  end  of  which  the  bile  pig- 
ment was  found. ij:      Even  this  observer  found   no  bile 
pigment  after  a  six-hours  narcosis  from  chloroform. 
Although   Breschet  was  the  first  to  found  the  doc- 

*  Naunyn,  op.  cit.  p.  438. 

t  But  this  does  not  explain  the  matter  throughout :  Nothnagel  used  rabbits  in 
all  his  experiments  with  a2ther  and  chloroform  {Berlin,  klin.  Wochcnschy.  1866 
p.  31)  and  Kiihne  {Lchrh.  dcr  phys.  Chcmic,  p.  89)  expressly  says  that  rabbits  must 
be  used  in  the  haemoglobin-injection  experiment  on  account  of  the  constant  pre- 
sence of  the  bile  pigment  reaction  in  the  urine  of  dogs. 

+  Tarchanoff,  Arch.f.  d.  gcs.  Phys.  1874,  Bd.  ix.  p.  53. 


of  H cematogenous  Jaundice.  237 

trine  of  a  haematogenous  jaundice,  supported  by  Andral, 
and  more  lately  by  less-known  names,  yet  the  theory 
seems  to  have  made  little  progress  in  France  ;  and 
in  England  the  doctrine  is  but  little  received,  the 
other  view,  that  of  jaundice  from  suppression,  find- 
ing greater  favour.  It  is  chiefly  invoked  to  explain 
the  phsenomena  of  icterus  gravis.  Under  this  head  may 
be  placed  acute  yellow  atrophy  of  the  liver,  the  jaundice 
seen  in  poisoning  from  phosphorus,  in  pyemia,  and 
other  acute  diseases.  In  this  way  Leyden  has  laboured 
to  explain  the  yellowness  of  the  skin  sometimes  seen  in 
chlorosis,  pyaemia,  heart  disease,  or  after  anaesthesia 
from  chloroform.  In  these  cases  the  yellowness  of  the 
skin  is  out  of  all  proportion  greater  than  the  bilious  ap- 
pearance of  the  urine.  In  jaundice  from  obstruction, 
the  reverse  is  seen.  There  is  likewise  no  evidence  of 
the  presence  of  bile  acids  in  the  urine  in  these  cases. 
Further,  there  is  often  proof,  in  the  cases  of  icteriis 
gravis,  of  the  circulation  of  some  poison  in  the  blood, 
able  to  destroy  the  red  corpuscles,  as  in  poisoning  by 
phosphorus,  yellow  fever,  and  the  like.  The  varieties 
of  icterus  gravis  resemble  each  other  in  having  a  ten- 
dency to  stupor  or  delirium.  In  the  fatal  cases,  no  im- 
pediment can  be  found,  after  death,  to  the  flow  of  bile 
into  the  duodenum,  the  liver  itself  being  free  from  a 
jaundiced  tint  and  the  faeces  containing  bile.  A  far 
advanced  fatty  degeneration  of  all  the  glandular  and 
muscular  organs  is  likewise  found.* 

I  should  long  hesitate  in  forming  any  opinions  from 
the  statement  that  the  urine  is  often  less  jaundiced 
than  the  skin,  or  that  the  liver  after  death  shows  no 
jaundiced  appearance.  Virchow,  for  instance,  for- 
merly thought  that  a  jaundice  of  the  liver  preceded 
a  jaundice  of  the  whole  body,*!*  but  later  saw  reasons 

*  Leyden,  Beitrdge  ziiv  Pathologic  des  Icterus,  Berlin,  1866,  p.  6. 
f  Virchow,  Arch.  f.  path,  Anat.  1847,  Bd.  i.  p.  380. 


238  Discussion  of  the  Theory 

to  withdraw  this  opinion,*  and  this  admission  is  of  the 
greater  importance,  since  Virchow  was  undoubtedly 
the  founder  in  modern  times  of  the  doctrine  of  hcema- 
togenous  jaundice.  Nor  can  I  attach  much  weight 
to  the  statement,  that  in  cases  of  shght  jaundice,  the 
urine  is  much  less  jaundiced  than  the  skin.  I  have 
sometimes  found  in  examining  cases  of  slight  jaun- 
dice after  death,  that  the  serous  effusions  from  the 
chest  and  belly  gave  an  intense  reaction  with  nitric 
acid,  while  the  urine  gave  but  slight  indications  of  the 
presence  of  bile  pigment  with  the  same  reagent.  The 
serous  effusions  and  the  urine  may,  I  should  think,  be 
looked  upon  as  at  least  equal  in  importance  for  indi- 
cating the  amount  of  bile  pigment  contained  in  the 
blood.  The  cases  which  I  mention  have  been  chiefly 
those  of  heart  disease. 

A  point  of  which  much  importance  has  been  made  by 
Leyden,  is  the  absence  of  the  bile  acids  in  the  urine,  in 
some  cases  of  jaundice.  Naunyn's  observations  have, 
however,  destroyed  all  value  which  may  be  attached  to 
this  opinion,  for  he  has  shown  that  the  bile  acids  may 
be, found  in  every  urine,  even  in  that  of  perfect  health. f 
They  appear  to  be  absent  in  no  cases  of  jaundice,  ex- 
cept perhaps  at  the  end  of  cases  of  long  continued 
obstruction  to  the  bile  ducts,  as  Golowin  has  pointed 
out.J 

It  is  indeed  only  from  the  fatal  cases  that  any  safe 
conclusions  can  be  drawn.  The  fatal  cases  of  which 
Leyden  speaks  all  belong  to  the  class  of  icterus  gravis. 
Poisoning  by  phosphorus  would,  I  think,  be  accepted 
as  a  type  of  this  class.  The  stools  are  sometimes 
coloured,    sometimes   free    from    colour.       Yet    Oskar 

*  Virchow,  Arch  f.  path.  Anat.  1865, Bd.  xxxii.  p.  121. 
f  Naunyn,  Arch.  f.  Anat.  und  Phys.  1868,  p.  430. 
X  Golowin,  Arch./,  path.  Anat.  1871,  Bd.  liii.  p.  433, 


of  HcBmatogenous  Jaundice.  239 

Wyss*  and  Ebsteinf  found  in  the  livers  of  dogs  and 
men  poisoned  by  phosphorus,  that  the  finer  ducts 
within  the  Hver  were  plugged  with  a  colourless  mucus 
which  hindered  the  descent  of  the  bile  ;  a  plain  cause 
of  jaundice.  While  this  explanation  of  the  jaundice 
remains  available,  it  seems  to  me  imprudent,  to  say  the 
least,  to  search  for  other  and  less  likely  causes  else- 
where. 

The  presence  of  deeply  coloured  stools  cannot  always 
be  received  as  proof  of  the  freedom  of  the  he-patic 
ducts.  Indeed,  in  jaundice,  the  more  deeply  coloured 
the  stools,  the  greater  suspicion  should  be  aroused.  It 
is  well  known  that  many  substances  given  by  the 
mouth  make  the  stools  dark,  as  charcoal,  iron,  or  bis- 
muth. What  is  more  important  in  the  present  discus- 
sion is  that  blood  passed  into  the  alimentary  canal 
causes  the  stools  to  have  a  very  high  colour ;  now  in 
icterus  gravis  haemorrhages  are  very  common  and  espe- 
cially abundant  in  the  stomach  and  intestines.  It  is 
therefore  not  surprising  to  find  that  in  many  cases  the 
stools  are  reported  to  be  dark.  In  a  case  of  my  own, 
I  found  that  the  faeces  in  the  large  intestine  were  clay- 
coloured  ;  in  the  small  intestine  they  were  dark,  almost 
black.  In  jaundice  I  look  upon  the  absence  of  colour 
in  the  stools  as  tolerable  proof  that  some  of  the  bile 
ducts  are  obstructed  ;  but  I  cannot  accept  the  presence 
of  colour  in  the  stools  as  proof  that  the  ducts  are  free. 

As  Leyden  has  been  the  champion  of  haematogenous 
jaundice  in  Germany,  so  Gubler  has  been  in  France.  In 
1857  h^  published  a  case  of  poisoning  by  lead,  compli- 
cated with  jaundice.  The  urine  was  very  high  coloured, 
and  to  the  eye  alone  presented  precisely  the  appearance 

*  Oskar  Wyss,  Arch.  d.  Heilkunde,  1867,  p.  469. 

-f  Ebstein,  ibid.  p.  506;  and  i86g,  p.  379.  I  have  myself  verified  the  statement 
that  the  smaller  ducts  may  hold  bile,  the  larger  a  colourless  fluid.  {Trans,  of  the 
Path.  Soc.  1874,  Vol.  XXV.  p.  161.) 


240  Gubler's  hcBmaphoeic  Jaundice. 

of  ordinary  jaundiced  urine.  It  gave,  however,  no  dis- 
tinct reaction  with  Gmehn's  test,  and  Gubler  from  this 
single  circumstance  calls  the  case  one  ofictere  hemophei- 
que*  There  is,  strange  to  say,  no  account  of  the  state 
of  the  stools  ;  so  the  case  proves  nothing.  The  same 
strange  disregard  of  an  important  appearance  runs 
through  the  table  of  elaborate  distinctions  given  by 
Michel,  a  pupil  of  Gubler,  the  theory  of  which  may  be 
at  any  moment  upset  by  an  inspection  of  the  fceces 
alvince.'\  The  cause  of  this  kind  of  jaundice  is,  according 
to  Gubler,  the  inability  of  the  liver  to  separate  from  the 
blood  the  colouring  materials  for  the  formation  of  bile, 
when  from  some  cause  or  other  there  is  too  rapid  de- 
struction of  the  red  globules.  This  blood  pigment,  free  in 
the  blood,  Gubler  calls  hsemophsein.J  This  is  evidently 
a  revival  of  the  old  doctrine  of  suppression,  allying 
itself  to  the  newer  theory  of  hsematogenous  jaundice. 
It  is  used  to  explain  the  jaundice  in  febrile  disorders  and 
of  the  new  born,  as  well  as  that  which  follows  catarrh  of 
the  stomach. §  Gerhardt  endorses  many  of  Gubler's 
opinions.       He  calls  the  pigment  in  the  urine  urobilin, 

*  Gubler,  Union  vied.  1857,  p.  503.  Haemaphsin  is  the  name  used  by  Franz 
Simon  for  the  natural  colouring  matter  of  the  urine,  and  which  he  believed  to  be 
derived  from  the  red  blood  corpuscles.  {Animal  Chemistry,  Sydenham  Society's 
Translation,  1845,  Vol.  i.  p.  159,  and  Vol.  ii.  p.  119.) 

f  Evariste  Michel,  de  I'ictere  hemapheiqne,  These  de  Paris,  1868,  pp.  14,  16,  and 
18.  In  the  cases  there  is  also  no  word  about  the  stools.  Dreyfus-Brisac,  another 
disciple  of  Gubler's,  does  indeed  at  the  end  of  his  table  of  distinctions  mention  that 
the  stools  in  hsemaphceic  jaundice  are  :  tres-variables,  parfois  un  peu  decolorees, 
le  plus  souvent  tres-colores ;  [De  Victere  hemapheiqne,  Paris,  1878,  p.  40)  but  in  his 
cases  he  seems  to  have  paid  very  little  attention  to  the  stools  at  the  height  of  the 
disease,  and  only  when  the  jaundice  is  fading  does  he  remark  how  deeply  coloured 
they  are ;  a  state  which  may  readily  be  explained  without  resorting  to  Gubler's 
hypothesis. 

+  Rendu  gives  a  just  account  of  Gubler's  views  in  an  excellent  article  in  the 
Dictionnaire  encyclopediqite  dcs  Sciences  mid.  Foie  (pathologic)  46  Serie  t.  ii.  p.  680. 

§  Laborde  praises  Gubler  highly :  "  M.  Gubler,  il  faut  bien  le  dire,  I'a  faite 
completement  sienne  par  la  precision  apportee  dans  I'analyse  des  faits,  I'exacte 
appreciation  des  phenomenes,  et  les  developpements  qu'il  n'a  cesse  de  lui  donner, 
en  prenant  pour  base  les  faits  cliniques."  {Physiologic  patlivlogiqne  de  Victere, 
These  pour  I'agregation,  Paris,  i86g,  p.  69.) 


Poncefs  traiLmatic  Jaundice.  241 

but  solely  because  the  extract  of  the  urine  with  chlo- 
roform gives  a  fluorescence  into  green-yellow  when 
treated  with  choride  of  zinc  and  ammonia.* 

Poncet  has  also  published  a  thesis  in  which  he 
attempts  to  establish  a  jaundice  from  the  destruction  of 
the  blood  corpuscles  after  great  extravasations  of  blood. 
This  observer  is  of  opinion  that  hasmatogenous  jaun- 
dice can  no  longer  be  denied.  He  has  seen,  after  great 
extravasations  of  blood  in  the  limbs  or  trunk,  a  slight 
jaundice  arise.  This  jaundice  he  says  is  due  to  the 
destruction  of  the  red  corpuscles,  and  the  increased 
colour  of  the  urine  is  due  solely  to  an  increase  of  the 
urobilin.  Nothing  here,  too,  is  said  of  the  state  of  the 
stools.  Poncet  only  brings  forward  one  case  examined 
after  death  ;  and  in  this,  strange  to  say,  no  account 
of  the  liver  seems  to  be  recorded. f  This  writer  adds 
but  little  to  the  evidence  already  given  in  favour  of 
haematogenous  jaundice :  and  a  word  of  warning  has 
been  addressed  to  him  by  Paul  Cazeneuve  who 
could  find  no  increase  of  the  colouring  matters  of  the 
urine,  nor  any  bile  pigments  in  the  urine  after  the 
subcutaneous  injection  into  a  rabbit  of  10  to  20  C.  C.  of 
blood,  or  '05  to  'i  grm.  of  hcematin.;|: 

The  following  case,  which  Immermann  calls  one  of 
haematogenous  jaundice,  is  certainly  well  worthy  of 
attention. 

Christian  Rupaner,  aged  23,  born  in  Baden,  was 
admitted  into  the  Hospital  at  Basel  on  January  23. 
1873.  For  eleven  days  before,  he  had  been  suffering 
from  symptoms  of  a  moderately  severe  attack  of  typhoid 
fever.  The  course  of  the  disease  was  regular  and  un- 
complicated ;  it  was  treated  with  quinine  in  large  doses^ 

*  Gerhardt,  Correspondenz-Bldtfcr  des  aUgem.   aeraf.   Vcrcines  von  Thi'iriiigen, 
1878,  Jahrg.  vii.  No.  ii.  Nov.  20. 

f  A.  Poncet,  de  Victere  hematique  traumatique.  These  de  Paris,  1874,  p.  40, 
X  p.  Cazeneuve,  Gaz.  mcd.  de  Paris,  1877,  p.  271, 

R 


242  Immermann^s  case  of  Jaundice. 

and  with  baths  as  often  as  the  temperature  rose.  On  Feb. 
21.  there  was  a  relapse,  treated  as  the  first  attack.  On 
Feb.  27.  the  urine  was  sHghtly  albuminous  and 
contained  pus  cells.  On  March  ist  a  slight  jaundiced 
tint  began  about  7  a.m.  and  at  g.  a.m.  the  tint  was  deep  ; 
liver  natural.  Continual  vomiting  of  bilious  matter  and 
two  highly  bilious  stools  in  the  course  of  the  morning. 
At  the  same  time  the  urine  was  scanty  and  almost 
black.  It  gave  no  trace  of  bile  pigment,  but  became 
almost  solid  on  boiling,  and  showed  Heller's  test  for 
blood.  Under  the  microscope  no  red  corpuscles,  only 
pus  corpuscles  were  seen.  On  March  2.  the  jaundice 
was  the  same ;  vomiting,  four  bilious  stools.  The 
urine  albuminous  as  the  day  before,  no  red  blood 
corpuscles  in  sediment  but  some  well  preserved  pus 
corpuscles.  With  the  spectroscope,  oxyhaemoglobin 
and  hasmatin  were  in  the  urine  ;  no  bile  pigment.  On 
March  3.  the  jaundice  of  skin  and  conjunctiva  much 
decreased.  Vomiting  continued  with  diarrhoea  and 
bilious  stools.  The  urine  yellow  brown,  highly  al- 
buminous, containing  neither  blood  colouring  matter 
nor  bile  pigment.  On  March  4.  jaundice  gone ; 
vomiting  and  albuminuria  continuing  till  death.  On 
March  g.  the  patient  died  comatose,  no  jaundice  and  no 
blood  in  water  being  again  seen.  After  death  the  kidneys 
were  found  in  a  state  of  acute  parenchymatous  degen- 
eration. In  the  small  intestine  bilious  fluid  ;  on  pressing 
the  gall-bladder,  a  hyaline  plug  escaped  from  the  gall 
ducts  into  the  duodenum.  The  lower  part  of  small  intes- 
tine showed  freshly-healed  typhoid  changes.  In  the  liver 
there  was  some  over  growth  of  the  connective  tissue.* 

The  reader  should  note,  in  forming  a  judgement  on 
this  case,  that  the  liver  and  the  ducts  were  not  free  from 
disease.     The  liver  was  in  an  early  stage  of  cirrhosis, 

•  Immermann,  Deiitsches  Arch./.  Idin.  Med.  1874,  Bd.  xii.  p.  502.      The  case  is 
fully  given.  « 


Jaundice  from  Suppression.  243 

and  the  extremity  of  the  gall  duct  held  a  plug  of  mucus. 
It  is  true  that  no  bile  pigment  was  found  in  the  urine, 
but  it  is  possible  that  the  large  amount  of  albumen  pre- 
sent in  the  urine  may  have  had  the  effect  of  masking 
the  ordinary  Gmelin's  reaction.  Bile  acids  were  not 
looked  for. 

The  grounds  on  which  the  theory  of  hsematogenous 
jaundice  have  been  set  up  are,  to  my  mind,  altogether 
insufficient.  It  cannot  be  said  that  the  origin  of  the  co- 
louring matter  of  the  bile  from  that  of  the  blood  is  proved  ; 
indeed  of  late  the  course  of  discovery  has  been  rather 
against  their  identity  than  in  favour  of  it.  And  until  it 
have  been  shown  that  bile  pigment  has  its  source  in  the 
blood-corpuscles,  it  will  be  the  duty  of  the  practical  phy- 
sician to  reject  the  theory  of  hsematogenous  jaundice. 

II.  The  second  kind  of  jaundice  is  that  of  jaundice 
by  suppression.  The  great  doctors  of  the  seventeenth, 
and  early  part  of  the  eighteenth,  centuries,  taught  that 
the  secretions  existed  ready  formed  in  the  blood,  and 
that  the  glands  merely  acted  as  filters  to  strain  the 
excretions  from  the  circulating  mass.  Glisson  speaks 
thus  of  the  liver.*  The  doctrine  of  jaundice  from  sup- 
pression of  the  secretion  was  a  natural  outcome  of  this 
physiology.  It  is  therefore  to  be  found  in  the  writings 
of  Morgagni,  who  distinctly  attributes  the  jaundice  in 
case  of  obstruction  not  to  the  absorption  of  bile  already 
secreted ;  but,  because  the  bile  ducts  are  already 
filled  by  secretion,  the  bile  cannot  enter  them,  and  thus 
accumulates  in  the  blood. f  Van  Swieten,  likewise, 
speaks  of  two  kinds  of  jaundice  ;  one  from  an  impedi- 
ment to  the  free  exit  of  the  bile  from  the  bile  ducts  ; 
the  other,  from  a  hindered  secretion. J  Towards  the 
end    of  the    eighteenth  century,  this  view  of  jaundice 

*  Glisson,  Altai.  Hepat.  Cap.  xxxviii.  et  scqq.  Amstelsedami,  1659. 

f  Morgagni,  Dc  scdihis,  cte.  Ep.  xxxvii.  Art.  g. 

:j:  Van  Swieten,  Coiiwunt.  §  950,  Lugd.  Bat.  1755,  t.  iii.  p.  127. 

R  2 


244  Jaundice  from  Sttppression. 

began  to  lose  ground,  even  before  the  experiments  of 
Saunders.  It  continued,  however,  to  be  taught  and 
acted  on  by  many  noted  physicians. 

Andral,*  Sir  Thomas  Watson,*]"  Bamberger, J  Gries- 
inger§  and  Trousseau||  have  all  supported  the  doctrine  of 
jaundice  by  suppression.  Dr.  Budd^  considers  this  kind 
of  jaundice  to  be  by  far  the  most  common.  He  believes, 
however,  that  the  colouring  matters  only  are  made  in  the 
blood,  while  the  bile  acids  are  formed  in  the  liver  itself; 
a  view  which  is  supported  by  Skoda**  and  Dr.  George 
Harley.ft  But  about  the  date  of  the  publication  of  the 
first  edition  of  Dr.  Budd's  book,  the  doctrine  of  the  forma- 
tion of  the  bile  in  the  blood  fell  into  discredit  with 
physiologists,  and  in  our  own  day,  with  the  exception 
of  one  or  two  supporters,  is  universally  disbelieved. 
With  this,  as  a  matter  of  course,  the  notion  of  a  jaun- 
dice from  suppression  of  secretion  fell  too. 

The  turn  of  the  tide  of  medical  opinion  may  be  noted 
when  Liebermeister,  fifteen  years  ago,  pointed  out 
that  he  did  not  think  the  doctrine  of  the  non-exist- 
ance  of  the  elements  of  the  bile  in  the  blood  so  surely 
proved  as  others  then  thought.  One  of  his  reasons  is 
that  jaundice  sometimes  breaks  out  after  the  liver  cells 
have    completely   disappeared. §§      There  is   no  proof, 

*  Andral,  Cliniquc  mcd.  Paris,  1839,  t.  ii.  p.  286. 

f  Thomas  Watson,  Lectures  on  the  Principles  and  Practice  of  Physic,  Lecture 
Ixxv.  London,  1857,  Fourth  ed.  Vol.  ii.  p.  602.  He  says  that  Darwin  was  the  first 
to  introduce  into  this  country  the  doctrine  since  supported  by  Chevreul  and  Mayo. 
Erasmus  Darwin  {Zoonomia,  Lond.  1801,  Vol.  ii.  p.  5)  speaks  of  a  paralysis  or 
inability  of  the  secretory  vessels  of  the  liver,  but  without  bile  in  the  stools  or  urine, 
and  a  skin  like  the  colour  of  full-grown  silkworms.  It  may  well  be  doubted  if  he 
speak  of  a  jaundice. 

%  Bamberger,  Krankhcitcn  dcs  chylopo'ctischcn  Systems,  Erlangen,  1857,  p.  517. 

§  Griesinger,  Infcclionskrankhcitcn,  Erlangen,  1857,  P-  78- 

II  Trousseau,  CUnique  mcd.  dc  VHotcl  Dicu,  Paris,   1865.  2e  ed.  t.   iii.   p.  274. 
His  opinions  expressed  elsewhere  make  it  doubtful  if  he  always  held  this  belief. 
•51  George  Budd,  On  Diseases  of  the  Liver,  London,  1845,  p.  373. 

**  Skoda,  Deutsche  Klinik,  1859,  p.  286. 

tf  George  Harley,  Jaundice,  London,  1863,  p.  20. 

\X  Liebermeister,  Beitrdge  zur  path.  Anat.  n.  Klinik  d.  Leherhrankhciten,  Tubin- 
gen, 1864,  p.  241. 


Jaundice  from  Stippression,  245 

however,  that  this  statement  of  Liebermeister's  is  cor- 
rect. No  doubt  he  has  shown  that  in  a  large  number 
of  cases,  hitherto  unsuspected,  the  hver  cells  are  de- 
stroyed ;  in  many  cases  of  pyaemia,  puerperal  and 
typhoid  fever :  but  I  do  not  think  he  has  proved  that 
the  jaundice  has  ever  arisen  after  the  complete  destruc- 
tion of  the  secreting  tissue  of  the  liver.  Som.e  writers 
have  thought  that  acute  yellow  atrophy  affords  the  best 
proof  that  the  bile  is  made  in  the  liver,  because  towards 
the  end  of  the  disease,  as  the  liver  cells  are  destroyed, 
but  little  pigment  is  found  in  the  urine,  and  no  bile 
acids.* 

Dr.  Moxon  thinks  that  the  colourless  contents  of  the 
ducts  in  cases  of  long  continued  obstruction  prove  that 
the  bile  is  not  formed  in  the  liver,  and  that  all  cases  of 
jaundice  are  caused  by  suppression  of  the  secretion, 
not  by  reabsorption  of  secreted  bile.f  His  views  closely 
resemble  those  of  Morgagni  quoted  above,  but  it  cannot 
be  thought  that  he  has  brought  forward  much  evidence 
in  favour  of  his  belief, 

Jaccoud  is  inclined  to  the  belief  that  in  long-continued 
jaundice  the  liver  ceases  to  secrete  bile. J  To  this  view 
there  is  but  little  physiological  objection  ;  for  it  is  not 
improbable  that  a  liver  severely  damaged  should  cease 
to  secrete  bile,  and  that  the  jaundice  should  thereupon 
decrease.  It  is  very  different  to  the  statement  that 
jaundice  may  be  caused  by  suppression  of  the  functions 
of  the  liver. 

The  theory  that  the  bile  was  not  formed  by  the  liver 
was  thought  to  have  been  disproved  by  Johannes 
Mueller,  Kunde,  and  Moleschott§.  This  last  observer 
found  that  frogs,  after  their  liver  had  been  taken  away, 


•  Hilton  Fagge,  Guy''s  Hospital  Reports,  1875,  p.  174. 

f  Moxon,  Titans,  of  the  Pathological  Society  of  London,  1873,  Vol.  xxiv.  p.  133. 

X  Jaccoud,  Lcgons  de  Clinique  med.  (Lariboisiere)  Paris,  1873,  p.  543. 

§  See  p.  83  of  this  work. 


246  Secretion  or  Excretion  of 

lived  nearly  three  weeks,  and  yet  no  trace  of  bile  could 
be  found  in  the  blood,  muscles,  gastric  juice,  lymph, 
or  urine.  The  vital  processes  in  these  cold-blooded 
animals  are,  however,  but  slow.  Leyden  tied  the  com- 
mon duct  of  frogs,  and  after  8  to  14  days  found  no  trace 
of  jaundice  in  the  liver,*  so  that  if  no  jaundice  be  caused 
by  ligature  of  the  common  duct,  it  would  not  be  strange 
that  none  should  arise  after  the  taking  out  of  the  liver. 
If  these  experiments  of  Leyden's  be  trustworthy,  a  very 
important  support  to  the  view  that  the  liver  forms  the 
bile  is  taken  away. 

Another  fact  thought  to  favour  this  last  view  is  that 
the  bile  acids  and  bile  pigments  cannot  be  found  in  the 
blood,  even  in  the  blood  of  the  portal  vein.  Of  this  last 
there  is  usually  so  little  to  be  had  that  there  is  scarcely 
enough  for  a  trustworthy  analysis.  But  I  believe  that 
no  observer  in  modern  times  has  been  able  in  health 
with  certainty  to  detect  any  of  the  elements  of  the  bile 
in  the  blood.  Naunyn,  however,  has  found  small  but 
appreciable  amounts  of  bile  acids  in  the  urine  of  healthy 
men  :f  and  it  is  no  uncommon  thing  to  find  that  the 
urine  of  men  and  dogs  shows  traces  of  the  presence  of 
bile  pigment :  and  this  is  especially  the  case  after  long 
fasting,  when,  that  is  to  say,  the  liver  has  not  for  some 
time  been  stimulated  to  excrete  much  bile.  It  may 
further  be  alleged  that  if  the  elements  of  the  bile  be 
formed  in  the  blood,  it  would  be  unlikely  that  they 
should  be  found  in  the  serum.  The  liver  seems,  as 
shown  by  the  experiments  quoted  just  above,  to  have 
the  power  of  rapidly  secreting  into  the  bile  ducts  all  the 
bile  pigment  and  bile  acids  which  may  be  brought  into 
the   blood.      On  the  other  hand  it  may  be  pointed  out 

*  Leyden,  Beitrdge  ziir  Path,  dcs  Icterus,  Berlin,  1866,  p.  ig.  He  does  not, 
however,  expressly  say  that  he  examined  the  blood  or  urine ;  nor  does  he  say  that 
he  fed  the  animals,  a  point  of  importance  in  judging  of  matters  allied  to  the  diges- 
tion and  general  powers  of  life. 

f  Naunyn,  Arch.f.  Anat.  u.  Phys.  1868,  p.  430. 


the  Bile  by  the  Liver.  247 

that  Schmulewitsch  has  succeeded  in  keeping  up  a  con- 
tinuous secretion  of  bile  for  two  or  more  hours  after 
death  by  causing  the  same  blood  to  pass  and  repass 
many  times  through  the  liver,  a  phsenomenon  opposed 
to  the  notion  that  the  bile  is  simply  separated  by  the 
liver.*  Pfliiger  has,  however,  repeated  Schmulewitsch's 
experiments  in  a  dead  liver  with  three  per  cent,  saline 
solution,  and  has  found  an  apparent  abundant  secretion 
of  bile.  He  thinks  there  is  no  real  secretion  of  bile,  but 
a  transudation  into  the  ducts  pushing  the  bile  already 
made  before  it.f  Rohrig  has  repeated  both  Schmule- 
witsch's and  Pfliiger's  experiments,  and  finds  that  bile  is 
secreted  when  blood  is  passed  through  the  vessels,  while 
none  flows  out  when  saline  solution  is  ussd.J 

The  presence  also  of  a  small  quantity  of  the  bile 
pigments  and  bile  acids  in  the  urine  may  be  explained 
by  supposing  that  they  have  been  absorbed  from  the 
bile  passages  after  secretion.  Such  was  the  belief  of 
Dr.  Bence  Jones, §  who  says  that  the  bile  begins  to  pass 
out  of  the  gall  bladdder  as  soon  as  it  is  passed  into  it. 
Of  this  statement  it  must  be  admitted,  however,  that 
very  little  direct  proof  exists. 

Some  authors,  especially  Dr.  Murchison,||  have 
looked  upon  the  fact  that  in  some  cases  of  diseased 
livers  without  jaundice,   no  bile   can  be  found   in   the 

*  Schmulewitsch,  Arbeitcn  aus  dcr  phys.  Anstalt  Z2i  Leipzig,  iii.  Jahrg.  1868, 
p.  113. 

f  Pfliiger,  Arch,  f.  d.  ges.  Phys.  1871,  Bd.  iv.  p.  54. 

J  Rohrig,  Strieker's  Med.  jfahrbb.  Wien,  1873,  p.  267. 

§  Bence  Jones,  St.  George^s  Hasp.  Reports,  1866,  Vol.  i.  p.  190. 

II  Murchison,  Clinical  Lectures  on  Diseases  of  the  Liver,  London,  1S68,  p.  305. 
I  think  these  cases  of  colourless  mucus  in  the  bile  passages  without  jaundice  are 
somewhat  rare.  Upon  Haspel's  cases  {Maladies  de  VAlgerie,  Paris,  1850,  t.  .i. 
p.  262)  I  think  much  weight  can  scarcely  be  laid.  He  is  speaking  of  abscess  of 
the  liver  in  which  there  was  almost  complete  destruction  of  the  organ.  He  adds 
that  the  bile  was  no  longer  secreted,  and  the  bladder  contained  only  a  little  white 
.  mucus.  He  does  not  speak  of  the  state  of  the  other  bile  passages.  See  also 
cases  reported  by  Andral,  {Clinique  tned.  Paris,  1839,  t.  ii.  p.  275.)  Frerichs,  {op. 
cit.  Bd.  i.  pp.  86  and  322.)  and  Wertheimber.  {Fragmente  ziir  Lelire  voin  Icterus^ 
Miinchen,  1854,  p.  3.) 


248  Gubler^s  theory  of  a 

bile  ducts,  as  evidence  in  favour  of  the  view  that  the 
bile  is  formed  in  the  liver.  Dr.  Hilton  Fagge,  in  a 
paper  lately  published,*  admits  that  this  would  be  good 
evidence,  were  the  liver  diseased  in  all  the  cases  in 
which  the  bile  ducts  were  unstained.  He  then  quotes 
Dr.  Moxon's  authority  for  saying  that  in  only  one  out 
of  four  such  cases  observed  by  him,  was  the  liver  dis- 
eased,"j*  the  other  three  being  cases  of  pyaemia  and 
pneumonia.  The  liver  is  so  commonly  diseased  in 
these  two  morbid  states,  and  as  commonly  overlooked, 
that  it  would  be  desirable  to  have  further  evidence  as  to 
the  state  of  the  liver,  before  deciding  that  the  liver  is 
not  always  diseased  when  the  ducts  are  free  from  colour. 

Gubler,  according  to  his  interpreter  Michel,  appears 
to  have  formulated  a  theory  of  jaundice  which  unites 
the  idea  of  suppression  of  the  functions  of  the  liver  with 
a  change  in  the  blood,  Michel,  giving  inedited  tables 
of  Gubler'SjJ  says  :  "  The  exciting  cause  of  h^maphaeic 
jaundice  is  an  inability,  absolute  or  relative,  of  the 
liver  to  separate  from  the  blood  the  materials  destined 
for  the  formation  of  bile,  and  especially  the  colouring 
matter  derived  from  the  destruction  of  the  globules  and 
to  which  Gubler  gives  in  general  the  name  of  haema- 
phaein.  The  proportion  of  this  colouring  matter,  the 
source  of  that  of  the  bile,  being  normal,  the  liver 
sometimes  falls  into  a  state  of  torpor,  or  the  liver  con- 
tinuing its  functions,  the  destruction  of  the  globules  be- 
comes sometimes  excessively  rapid,  and  brings  into  the 
circulation  waste  material  which  the  liver  cannot  trans- 
form. 

**  The  remote  causes  of  this  kind  of  jaundice  would 

*  Hilton  Fagge,  Guy's  Hospital  Reports,  1875,  p.  172. 

f  Moxon,  Trans,  of  the  Path.  Soc.  of  London,  1869,  Vol.  xx.  p.  220. 

+  Apparently  derived  from  aT/icc  and  ipaios,  dusky  dun,  grey,  Latin  fuscus.  (See 
Simon,  Animal  Chemistry,  1845,  Sydenham  Society  Trans.  Vol.  i.  p.  42.) .  Ictere 
hemopheique  appears  as  the  title  of  a  case  by  Gubler  in  the  Union  vied,  for  1857, 
P-  503- 


Jaundice  from  SiLppression.  249 

thus  be  those  which  paralyse  the  secreting  functions  of 
the  Hver,  either  by  preventing  the  bringing  to  this  organ 
of  materials  upon  which  it  acts,  or  by  striking  the  pa- 
renchyma with  inertia.  Thus  hsemaphseic  jaundice  is 
seen  most  commonly  in  acute  phlegmasiae  with  rapid 
destruction  of  the  red  corpuscles  :  such  as  pneumonia, 
acute  rheumatism,  in  poisonings,  such  as  yellow  fever, 
pyaemia,  agues  :  in  the  embarras  gastrique  and  the  jaun- 
dice of  the  new  born." 

Gubler,  according  to  the  same  author,  looks  upon 
the  following  appearances  as  diagnostic  of  this  variety 
of  jaundice,  as  distinguished  from  that  caused  by  a 
hindrance  to  the  flow  of  bile  :  The  tint  of  the  patient 
slight,  sometimes  deep,  but  in  every  case  a  little  dull ; 
no  itching  or  exanthemata  ;  the  serum  of  the  blood  and 
closed  cavities,  when  acted  on  by  nitric  acid,  shows  a 
brown  colour ;  the  slow  pulse  is  but  a  temporary  symp- 
tom, seen  in  convalescence  ;  the  urine  is  an  amber  red 
or  like  strong  tea  ;  it  stains  linen  reddish  ;  which,  when 
dried,  is  of  the  colour  of  salmon  or  weak  rhatany  decoc- 
tion ;  of  feeble  dyeing  power  ;  nitric  acid  gives  a  colour, 
more  or  less  deep,  of  brown  red,  and  gives  no  precipi- 
tate of  biliary  resin,  ordinarily  taken  for  albumen.* 

The  views  of  Gubler  seemed  to  have  been  based  on  a 
case  of  lead  colic,  in  which  jaundice  was  a  well-marked 
symptom. t  It  is  therefore  the  more  noteworthy  that, 
in  this  case,  upon  which  so  much  depends,  no  record 
should  appear  of  the  state  of  the  stools.  The  views  of 
this  observer  seem  to  me  so  crude  and  ill-digested  that 
I  do  not  think  it  will  be  worth  while  further  to  discuss 
them. 

It  will  be  seen  that  very  little  evidence  as  to  the  place 
in  which  the  bile  pigments  and  bile  acids  are  formed  is 

*  Michel,  De  Victere  hemapheique,  These  de   Paris,   1868,  pp.    14,  16,   and  iS. 
Of.  Laborde,  Physiologic  pathologique  de  Victere,  These  de  Paris,  1869,  p.  91. 
f  Gubler,  Union  mi'd.  1857,  P-  S^S- 


250  Jaundice  from  absorption 

in  existence  ;  but  that  what  little  evidence  there  is  may 
be  cited  in  favour  of  the  view  that  these  bodies  are 
formed  in  the  liver.  This  being  the  case,  physicians 
have  no  right  to  found  a  theory  of  jaundice  which  de- 
mands a  contrary  physiological  theory,  for  theories  in 
medicine  must  be  framed  in  consonance  with  those  views 
for  which  there  is  the  greater  evidence. 

III.  The  third  theory  of  jaundice  is  that  which  attri- 
butes this  symptom  to  the  absorption  into  the  blood  of 
bile  already  excreted  by  the  liver.  It  is  beyond  all 
doubt  the  best  founded  of  the  theories  of  jaundice  ;  and 
the  one  to  which  the  morbid  anatomist,  as  well  as  the 
experimental  pathologist,  will  be  the  most  inclined  ;  as 
in  the  great  majority  of  cases  of  jaundice  which  are 
examined  after  death,  some  obstruction  to  the  flow  of 
bile  into  the  duodenum  is  undoubtedly  found. 

It  has  been  seen  that,  very  early  in  the  history  of 
medicine,  obstruction  to  the  bile  ducts  was  looked  upon 
as  a  cause  of  jaundice.  No  distinction,  however,  was 
made  between  the  effects  of  an  obstruction  to  the 
hepatic  and  the  cystic  duct ;  and  Morgagni  had 
to  teach  that  the  cystic  duct  could  be  obstructed 
without  jaundice  being  caused.  This  writer  did  not, 
however,  look  upon  the  absorption  of  secreted  bile  as 
the  cause  of  jaundice.  He  thought  that  the  bile  was 
unable  to  pass  from  the  liver  into  the  ducts,  these  being 
already  over- filled,  and  that  jaundice  was  caused  by 
suppression  of  secretion.  This  doctrine,  however,  was 
overthrown  at  the  end  of  the  last  century  by  the  experi- 
ments of  Saunders.  He  threw  a  ligature  around  the 
bile  duct  of  a  dog  ;  it  was  killed  in  two  hours  after.  A 
bilious  coloured  fluid  was  seen  in  the  absorbents  around 
the  parts  and  near  the  thoracic  duct.  The  serum  of 
the  blood  taken  from  the  jugular  vein  gave  a  yellow 
tinge  to  white  paper  dipped  in  it ;  much  less,  however, 
than  the    serum    from    the   hepatic   veins,    the  '  deeper 


of  Bile  already  secreted.  251 

colour  of  which  was  well-marked.*  From  these  two 
experiments  Saunders  thought  that  it  was  proved  that 
the  absorbents  as  well  as  the  hepatic  veins  are  con- 
cerned in  the  bringing  forth  of  jaundice. f 

For  nearly  a  hundred  years  this  theory  of  jaundice 
from  absorption  has  held  its  own,  and  been  assented  to 
by  every  physician  and  pathologist  who  has  written  on 
the  subject.  Among  the  theories  of  jaundice  it  is  the 
only  one  grounded  upon  observation  and  experiment, 
and  the  only  one  to  which  universal  assent  may  be  de- 
manded. 

The  kinds  of  jaundice  from  absorption  have  been 
described : 

i.  Jaundice  from  obstruction  of  the  ducts. 

ii.  Jaundice  from  absorption  of  the  bile  when  the 
pressure  in  the  blood-vessels  of  the  liver  is  decreased. 

iii.  Jaundice  from  incomplete  destruction  of  the  bile 
absorbed  into  the  blood. 

i.  It  is  well  known  from  the  experiments  of  Heiden- 
hain  that  the  pressure  under  which  bile  is  excreted  is 
extremely  small.  J  In  guinea  pigs,  the  bile  ceases  to 
flow  down  the  ducts  when  opposed  by  a  column  of 
water  only  20  centimeters  high,   and  prefers   to   pass 

*  Saunders,  A  Treatise  on  the  Structure,  Economy,  and  Diseases  of  the  Liver, 
London,  1803,  3rd  ed.  p.  iii. 

f  Lately  repeating  Saunders'  experiment,  I  was  unable  to  arrive  at  the  same 
results  as  he  did.  {St.  Bartholomew'' s  Hospital  Reports,  1873,  vol.  ix.  p.  176.) 
Frerichs  likewise  {op.  cit.  Bd.  i.  p.  99)  says  he  has  been  unable  to  discover  any  bile 
pigments  in  the  blood,  serum,  or  lymphatics,  twenty-four  hours  after  the  ducts 
have  been  tied.  Saunders  seems  to  have  tied  the  hepatic  duct;  in  my  own  experi- 
ment the  common  duct  was  tied.  I  have  no  doubt  of  the  general  accuracy  of 
Saunders'  conclusions. 

+  Friedlander  and  Barisch,  Arch.f.Anat.  Phys.  &c.  i860,  p.  666.  Kowalewsky 
(Pfliiger's  Arch.  f.  d.  ges.  Phys.  1874.  Bd.  viii.  p.  597.)  found  the  pressure  of  the 
bile  in  woorarised  cats  somewhat  higher,  from  12  to  20  mm.  of  mercury;  and  vary- 
ing, in  direct  ratio,  with  the  arterial  blood  pressure.  There  is  another  very  in- 
structive experiment  of  Heidenhain.  {Stud,  des  phys.  Instituts  zu  Brcslau,  1868. 
Heft.  iv.  p.  232.)  He  allowed  a  solution  of  indigo-carmine  to  flow  under  small 
pressure  into  the  bile  ducts :  the  mucous  membranes,  especially  the  conjunctiva, 
of  the  animal  soon  became  blue ;  the  urine  likewise. 


252  Jaundice  from  decreased  Pressure 

into  the  circulation.  It  will  be  seen  from  this  fact  how 
little  obstruction  to  the  passage  of  the  bile  into  the 
duodenum  is  needed  to  cause  the  bile  to  flow  back 
into  the  blood.  Nor  is  it  necessary  that  the  obstruc- 
tion should  be  complete,  but  merely  that  the  bore  of 
the  duct  should  be  narrowed  enough  to  cause  the  bile 
to  pass  with  some  trouble  into  the  bowel.  It  would 
almost  seem  that  the  bile  passes  as  readily  into  the  cir- 
culation as  into  the  duodenum.  Thus  jaundice  may 
easily  be  caused  by  a  hypersemic  or  catarrhal  swelling 
of  the  part  of  the  common  duct  which  passes  through 
the  walls  of  the  duodenum,  and  yet  after  death  all  trace 
of  swelling  will  have  disappeared,  and  the  duct  will  be 
fully  patent.  The  only  proof  of  the  existence  of  an 
obstruction  is  the  finding  of  the  part  of  the  duct  below 
the  obstruction  uncoloured  by  bile.  Even  this  evidence 
may  be  wanting  if  the  examination  have  not  been  made 
with  care  enough  ;  for  the  least  pressure  on  the  gall- 
bladder will  send  the  bile  down  the  common  duct  into 
the  bowel,  staining  the  duct  of  a  biHous  colour.  More 
obvious  causes,  such  as  the  presence  of  a  calculus  in 
the  duct,  or  the  pressure  of  a  tumour  from  the  outside, 
need  not  here  be  spoken  of. 

ii.  The  second  kind  of  jaundice  from  absorption  is 
that  which  takes  place  when  the  pressure  of  the  blood 
in  the  vessels  of  the  liver  is  decreased.  This  is 
Frerichs'  theory  of  jaundice.  He  says  that,  of  the 
two  products  of  the  liver  cells,  bile  and  sugar,  one 
passes  into  the  hepatic  vein,  the  other  into  the  capillary 
bile  ducts.  The  flow  of  fluid  towards  the  blood  can 
only  take  place  by  diffusion  ;  towards  the  bile  ducts,  by 
filtration.  How  the  two  are  separated  is  unknown. 
It  must  be  assumed  either  that  the  rapidity  of  the  dif- 
fusion into  the  blood  of  the  elements  of  the  bile  is 
greater  than  that  of  sugar  ;  or  that  the  sugar  has  some 
attraction  to  some  element  of  the  blood  which  is  want- 


of  the  Blood  in  the  Liver.  253 

ing  to  the  bile.  This  last  hypothesis  is  improbable, 
for  no  constituent  of  the  blood  is  known  to  possess 
an  attraction  for  sugar.  On  the  first  hypothesis,  the 
separation  of  the  two  substances  would  be  incomplete; 
some  of  the  bile  passing  into  the  blood,  and  some  of 
the  sugar  into  the  bile  ;  which,  indeed,  is  really  the 
case.*  If,  therefore,  the  pressure  of  the  blood  upon 
the  sides  of  the  vessels  in  the  liver  be  decreased,  the 
bile  will  pass  in  that  direction  where  there  is  least  re- 
sistance, that  is,  into  the  circulation,  and  thus  jaundice 
will  arise. t  Heidenhain  has  given  experimental  evi- 
dence of  the  truth  of  this  hypothesis.  He  found  that 
on  decreasing  the  pressure  of  the  blood  in  the  vessels 
of  the  liver,  the  bile  already  formed  began  to  pass  into 
the  circulation.  J  Frerichs  would  in  this  way  explain 
the  jaundice  seen  in  cases  of  plugging  of  the  portal 
vein,  in  cases  of  pigment  liver,  where  a  part  of  the 
capillaries  is  filled  by  masses  of  pigment,  the  jaundice 
seen  in  the  new-born,  and  after  bleeding  from  the  roots 
of  the  portal  vein,  as  in  yellow  fever.  This  theory  of 
jaundice  must  undoubtedly  be  allowed  a  place  equal  in 
probability  to  that  of  jaundice  from  obstruction.  It 
may  prove  serviceable  hereafter  in  explaining  the  jaun- 
dice which  so  suddenly  arises  after  mental  emotions, 
the  bites  of  serpents,  and  after  great  general  bleeding.  § 
iii.  The  last  theory  of  jaundice  which  remains  to  be 
discussed,  is  that  which  attributes  the  symptom  to  in- 
complete destruction  of  the  bile  absorbed  into  the  blood. 

*  C.  Ludwig,  Lehrb.  d.  Phys,  dcs  Mcnschen,  Leipzig  and  Heidelberg,  1856. 
Bd,  ii.  p.  232. 

f  Frerichs,  op.  cit.  Bd.  1.  p.  8g. 

%  Hedenhain,  Sttidien  des  phys.  Institnts  zii  Brcslau,  Leipzig,  186S.  Heft.  iv. 
p.  238. 

§  In  this  way  I  should  be  inclined  to  explain  the  jaundice  seen  in  the  two  first 
cases  recorded  by  Mr.  William  Smith.  {Brit.  Med.  youriial,  1869.  Vol.  ii.  p.  5.) 
The  jaundice  appeared  on  the  first  and  fifth  days  after  great  general  bleeding. 
The  stools  were  light  coloured.  In  the  two  last  cases  I  feel  scarcely  disposed  to 
connect  the  bleeding  with  the  jaundice. 


254  J aundice  from  defective  Decomposition 

In  health  the  greater  part  of  the  bile  pigment  and  bile 
acids  poured  into  the  duodenum  is  taken  up  again  dur- 
ing the  passage  of  the  food  through  the  small  intestine. 
The  bile,  therefore,  finds  its  way  into  the  radicles  of 
the  portal  vein,  and  undergoes  a  change  of  some  kind, 
probably  oxydation,  after  which  it  is  thrown  out  of  the 
system.  When  this  metamorphosis  of  the  bile  in  the 
blood  is  checked  or  brought  to  a  standstill,  jaundice 
comes  on. 

This  theory  may  be  found  in  the  writings  of  Daniel 
Sennert,  who  speaks  of  an  excess  of  bile  secreted  by 
the  liver,  which  cannot  be  excreted  by  the  accustomed 
passages.  In  this  disease,  he  says,  not  only  is  the 
urine  coloured  saffron,  but  the  faeces  are  also  highly 
coloured.  Fever  is  present  and  the  hands  and  feet  are 
hot.*  Distinct  traces  of  the  same  doctrine  may  be 
found  in  the  writings  of  Cullen,  who  regards  it  with 
disfavour  if  and  in  those  of  PortalJ  and  Gardien§  who 
approve.  Frerichs  had,  no  doubt,  some  such  theory  in 
mind  when  he  speaks  of  a  jaundice,  quite  independent 
of  the  liver,  caused  by  decreased  decomposition  and 
change  of  the  bile  in  the  blood.  He  rests,  however, 
too  much  upon  observations  which  are  now  known  to 
be  incorrect,  those  of  the  change  of  the  bile  acids  into  bile 
pigment.  II  The  late  Dr.  Murchison  may  be  looked  upon 
as  one  of  the  most  prominent  modern  defenders  of  this 
theory,  and  the  following  account  of  it  is  taken  from 
his  work.^ 

The  greater  part  of  the  bile  after  having  been  poured 
into   the  intestine  is  taken   up  by  the  radicles  of  the 

*  Dan.   Sennert,  Epitome  univcrsam  doclrinavi  snniina  fide  complectens,   edid. 
Bonetius,  Col.  Allob.  1655.  p.  681. 
f  Cullen,  First  Lines  of  the  Practiee  of  Physic,  §  1817. 

\  Portal,  Histoire  de  VAcademie  royale  des  Sciences,  1777,  Mhnoires,  p.  604. 
§  Gardien,  Traite  complet  d'accoucheinents,  Paris,  1816,  t.  iv.  p.  95. 
II  Frerichs,  op.  cit.  Bd.  i.  p.  94. 
^  Murchison,  Clinical  Lectures  on  Diseases  of  the  Liver,  Lond.  1868.  p.  375. 


of  Bile  absorbed  into  the  Blood.  255 

pOrtal  vein,  and  thus  passes  into  the  general  mass  of  the 
blood.  In  health,  the  bile  suffers  a  decomposition,  pro- 
bably an  oxydation,  and  is  cast  out  of  the  system  by  the 
lungs  or  kidneys.  But  in  some  diseased  states,  this 
change  does  not  take  place ;  and  the  bile  circulates 
with  the  blood,  causing  a  jaundice.  The  diseased  states 
which  hinder  these  changes  of  the  bile  from  taking 
•place  are:  i.  The  action  of  certain  poisons  on  the  ceco- 
nomy ;  they  are  chiefly  those  poisons  which  cause  an 
acute  parenchymatous  degeneration  of  the  glands  and 
muscles,  ii.  Nervous  influences,  as  fright,  iii.  Bad 
hygienic  conditions :  and  iv.  a  very  great  increase 
in  the  secretion  of  bile,  so  that  more  is  poured  out 
into  the  gut  than  can  be  taken  up  and  changed  in 
the  blood  into  colourless  material :  a  jaundice  therefore 
arises  from  the  circulation  of  bile  pigments  in  the  blood. 

This  theory  rests  for  support  chiefly  on  the  observa- 
tions of  Bidder  and  Schmidt  who  found  only  slight 
traces  of  bile  in  the  faeces  of  dogs.*  But  Hoppe-Seyler 
ten  years  after,  found  abundance  of  cholalic  acid  and 
undecomposed  biliary  acids  in  the  faeces  of  dogs.  He 
looks  upon  cholalic  acid  as  a  product  of  a  fermentation 
or  sort  of  digestion  of  the  bile  acids,  very  like  the  split- 
ting up  of  hippuric  acid  into  glycocoll  and  benzoic  acid 
in  decomposing  urine. f 

In  the  present  state  of  knowledge  it  cannot  be  said 
whether  the  whole  of  the  bile  secreted  be  at  once  cast 
out  of  the  body  or  not.  Schiff  and  his  followers  would 
say  that  the  greater  part  of  the  secretion,  bile  acids 
and  bile  pigment,  is  reabsorbed  into  the  blood,  and 
again  excreted  by  the  liver.  J 

Granting,  however,,  that  the  liver  has  this  power  of 


*  Bidder  and  Schmidt,  Die  Verdatmngssdfte  und  die  Stoffwechsel,  Mitau  and 
Leipzig,  1852,  p.  217. 
f  Hoppe,  Arch.  f.  path.  Anat.  1862,  Bd.  xxv.  p.  181 ;  1863,  Bd.  xxvi.  p.  535. 
X  See  p.  147  et  seqq.  for  a  discussion  of  this. 


25^  Jciundice  from  defective  metamorphosis. 

again  excreting  the  bile,  it  is  quite  unlikely  that  such 
absorption  of  bile  should  ever  become  the  cause  of  jaun- 
dice. For  all  the  bile  absorbed  by  the  vessels  is  at  once 
carried  by  the  portal  system  to  the  liver.  The  liver,  on 
the  showing  of  Schift*,  and  Tarchanoff,*)*  would  draw  to 
itself  the  bile  acids  and  bilirubin  in  the  blood,  and  forth- 
with excrete  them  in  the  bile.  Accepting  Schiff's  views 
then,  it  would  therefore  seem  most  likely  that  if  any  bile, 
acids  and  bile  pigments  were  absorbed  by  the  intestine, 
they  would  again  appear  in  the  bile  without  entering  the 
general  circulation  ;  and  without  entering  the  general 
circulation  no  jaundice  can  be  brought  about. 

The  only  instance  in  which  this  theory,  to  my  mind, 
can  be  entertained,  is  the  case  of  a  permanent  obstruc- 
tion of  the  circulation  through  the  portal  vein.  This 
vessel  has  been  artificially  obliterated,  and  traces  of 
the  bile  acids  and  bile  pigment  were  found  in  the  urine, 
traces,  however,  which  soon  disappeared.  J  It  is  known 
that  in  cases  of  thrombosis  of  the  portal  vein  jaundice  is 
a  common  symptom  ;  but  it  also  appears  to  be  a  per- 
manent, and  not  merely  a  passing  phaenomenon. 

*  Schiff,  Arch.  f.  d.  ges.  Pliys.  1870,  Bd.  iii.  p.  598  ;  and  Giorn.  di  Scienzc  nat. 
ed  econ.  Palermo,  1869,  Vol.  iv.  p.  g. 

f  Tarchanoff,  ibid.  1874,  Bd.  ix.  p.  332.  See  also  Feltz  and  Ritter,  journal 
de  VAnat.  et  de  la  Phys.  1870,  p.  315.  The  experiments  of  Huppert  [Arch.  d. 
Heilkundc,  1864,  p.  244)  and  of  E.  Bischoff  {Zcitsch if  t  f.  rat.  Med.  1864,  Bd.  xxi.  p. 
125)  would  seem  in  some  degree  to  be  against  Schiff  and  Heidenhain.  Huppert  after 
injecting  bile  acids  into  the  blood  found  only  a  fourth  or  a  third  excreted  by  the 
liver.  What  becomes  of  the  rest?  The  kidneys  do  not  excrete  them.  According 
to  Bischoff,  they  are  oxydised  in  the  blood.  This  power  of  oxydation  has,  how- 
ever, a  limit ;  this  limit  is  passed  in  jaundice,  and  bile  acids  appear  in  the  urine. 

;{:  Schiff,  of},  cit.  p.  6og. 


CHAPTER   XI. 

The  Symptoms  of  Jaundice. 

The  first  change  from  health  to  jaundice  is  seen  in  the 
colour  of  the  conjunctiva.  It  becomes  yellow.  This  is 
the  symptom  commonly  first  noticed  by  the  friends  of 
the  patient,  a  day  or  two  before  the  skin  has  changed 
its  hue.  In  the  lower  orders  it  may  often  be  found 
that  the  change  of  colour  in  the  face  is  the  first  to  draw 
attention,  the  yellowness  of  the  eyes  having  been  passed 
by.  With  the  better  classes,  the  eyes  are  commonly 
the  first  to  be  noticed.  When  the  eyes  show  the  first  ap- 
pearance of  yellowness,  however  slight  it  may  be,  the  urine 
will  also  give  a  good  reaction  with  Gmelin's  test,  showing 
the  presence  of  bile  pigment.  How  soon  these  symptoms 
set  in  after  the  obstruction  to  the  flow  of  bile  is  first  set 
up,  there  are  at  present  no  very  certain  means  of  judging. 
It  is  usually  said  that  they  appear  after  the  third  day  of 
obstruction  ;*  but  this  conclusion  is  drawn  from  obser- 
vations upon  dogs.  In  these  animals  the  conjunctiva 
has  a  brownish  appearance,  very  unlike  the  pearl  white 
of  a  human  sclerotic,  and  I  look  upon  this  as  a  hin- 
drance to  the  early  detection  of  changes  of  colour. 
From  observations  upon  men,  I  should  be  inclined  to 
put  the  first  appearance  of  jaundice  much  earlier  after 
obstruction ;  perhaps  within  the  first  twenty-four  or 
forty-eight  hours.  In  this  opinion  I  am  supported  by 
several  clinical  observers. f     The  serous  exudations  will 

*  Frerichs,  Klinik  d.  Leberkrankheiten,  Braunschweig,  1858,  Bd.  i.  p.  gg.  In 
my  own  experiments  upon  cats,  the  conjunctivae  did  not  become  discoloured  for 
many  days  after  the  operation.  {St.  Bartholomew's  Hasp.  Reports,  iSj 2,  Vol.  ix, 
p.  161.) 

f  Siebert,  Diagnostik  d.  Krankheiten  des  Unterleibes,  Erlangen,  1855,  p.  283. 
Audigne  {Gaz.  incd.  de  Paris,  1874,  in  Virchow  and  Hirsch's  jfahresb.f.  1874,  Bd. 
i.  p.  349)  found  that  bile  pigment  could  be  detected  in  the  urine  in  three  to  four 
hours  after  ligature  of  the  common  duct  of  a  dog.  As  the  urine  of  dogs  so  often 
contains  in  health  a  body  which  gives  a  reaction  precisely  similar  to  that  of  bile 
pigment,  this  observation  can  be  scarcely  looked  upon  as  conclusive. 

S 


258  Varying  Colours  of 

sometimes  after  death  give  a  reaction  with  Gmelin'vS 
test  when  little  or  no  trace  of  jaundice  exists  in  the 
skin. 

After  the  conjunctiva,  the  skin  of  the  face  becomes 
yellow.  At  first  it  may  be  no  more  than  a  sallow  tinge, 
hard  in  some  persons  to  tell  from  the  natural  tint  of  the 
skin.  This  is  especially  the  case  with  persons  of  dark 
complexion.  Those  who  are  fair  show  the  change 
earlier.  From  the  face  it  spreads  over  the  upper  part 
of  the  trunk  and  thence  over  the  belly  and  limbs,  the 
legs  being  the  last  to  show  the  yellow  tint. 

As  a  rule,  the  yellow  colour  of  the  skin  is  spread  all 
over  the  body,  no  part  being  more  deeply  stained  than 
the  other.  It  is,  however,  not  uncommon  to  see,  in 
cases  of  slight  jaundice,  the  upper  part  of  the  body 
yellow,  while  the  belly  and  legs  are  free  from  unnatural 
colour.  Frerichs  has  made  the  same  observation,* 
and  Hecker  has  noticed  a  case  of  acute  yellow  atrophy 
in  which  the  upper  part  only  of  the  body  was  coloured 
yellow. t  But  in  all  cases  of  severe  jaundice  which  have 
fallen  under  my  observation  the  whole  of  the  body  has 
been  nearly  equally  jaundiced. 

In  some  old  authors,  J  a  jaundice  limited  to  the  right 
half  of  the  body  and  of  the  face  and  hands  §  {icterus  dimi- 
diatus)  has  been  described.  I  scarcely  feel  able  altogether 
to  reject  these  statements  when  an  observation  of  a  like 
kind  has  been  recorded  by  so  credible  a  witness  as  Joseph 
Frank.      He  found   a  lady  to  have  at  first  jaundice  of 

*  Frerichs,  op.  cit.  Bd.  i.  p.  112. 

f  Hecker,  Monatsschriftf.  Geburtsk.  1863,  Bd.  xxi.  p.  212.  Cf.  van  Swieten, 
Comment,  §  950,  Lugd.  Bat.  1755,  t.  iii.  p.  141. 

I  Behrens,  Ephcmeridcs  Nat.  Cur.  Noriberg.  1715,  Centuria  iii.  obs.  Ixiv.  p.  145. 
An  old  man,  seized  with  right  hemiplegia,  had  jaundice  of  the  same  side  of  the 
body  as  the  hemiplegia :  the  right  side  of  nose  was  yellow,  the  left  natural  in  colour. 
Behrens  quotes  from  Ettmiiller  {op.  mod.  Francof.  ad  Moen.  1697,  ^-  •'•  P-  ^44)  ^ 
similar  case.  I  have  been  unable  to  verify  the  reference.  Morgagni  {De  sedibiis, 
etc.  Ep.  xi.  §  14)  mocks  at  Behrens'  account. 

§  Strack,  jfournal  dc  Mcdccine,  1768,  t.  xxviii.  p  163. 


the  Skin  in  Jaundice.  259 

the  right  side  only,  but  in  two  weeks  it  spread  over  the 
whole  body.*  This  observer  surely  possessed  as  good 
means  of  forming  an  opinion  on  this  point,  as  anyone 
at  the  present  day.  The  appearance  must,  however, 
be  extremely  uncommon,  one  of  the  rarest  phaeno- 
mena  in  medicine.  Peter  Frank  says  he  has  never 
seen  such  a  thing,  and  thinks  it  very  hard  to  explain  ;f 
in  which  every  one  who  is  able  to  form  an  opinion 
on  the  matter  must  agree  with  him.  Pouzol  attempts 
to  explain  it  by  bringing  into  notice  the  varying  vas- 
cular supply  of  different  parts  of  the  skin,  which  would 
cause  a  like  variation  in  the  supply  of  bile  pigment.  J 
This  may  serve  to  explain  some  cases  of  a  yellow  colour 
in  spots  [icterus  variegatus)  ;  these  have,  however,  still 
to  be  proved  to  be  jaundice.  It  does  not  explain  the 
appearance  of  jaundice  in  one  half  of  the  face  while  the 
other  half  remains  natural.  Morgagni  can  only  explain 
Behrens'  case  by  supposing  a  slowness  of  the  circulation 
in  the  paralysed  side  and  thus  no  time  being  given  to 
tinge  the  parts. § 

The  older  physicians  were  delighted  to  enumerate 
numberless  species  of  jaundice  according  to  the  amount 
of  bile  pigment  present  in  the  skin.  Aretaeus  describes 
two  species,  the  white  and  black,  melas  icterus,  a  word 
which  remains  in  use  in  our  own  day,  and  says  there  are 
myriads  of  stages  between  the  two.  ||  Many  of  the  so- 
called  species  of  jaundice  are  quite  different  diseases, 
icterus  albus,  ruber,  and  cceruleus  being  the  names  for 
chlorosis,  erythema,  and  cyanosis. 

The    mucous    membranes   do  not  share  in  the  yellow 


*  Joseph  Frank,  Praxeos  Medicce  nniversa  prcecepta,  Lips.  1843,  Part  iii.  Vol.  ii. 
Sec.  ii.  Fasc.  i.  p.  278. 

t  Peter  Frank,  De  ciirand.  horn,  inorb.  epitome,  Vienna,  1821,  Lib.  vi.  pars  iii. 
p.  308. 

I  Pouzol,  Essai  stw  Victcre,  Paris  1S72,  p.  63. 
§  Morgagni,  loc.  cit. 

II  Aretaeus,  De  cansis  ct  sigiiis,  Adams'  ed.  p.  83. 

S  2 


26o  Presence  of  Bile  Pigment  in 

tint  of  the  skin.  The  Hps,  for  example,  retain  the  redness 
of  health,  and  the  inside  of  the  mouth  shows  the  usual 
colour.*  A  yellow  colour  may  be  seen,  however,  if 
pressure  be  made  so  as  to  drive  all  the  blood  out  of  the 
mucous  membrane,  and  allow  the  tint  which  is  under- 
neath that  of  the  blood  vessels  to  appear.  There  is 
one  part  of  the  mucous  membrane  of  the  mouth,  that 
under  the  tongue,  which  is  often  yellow,  almost  con- 
stantly so,  an  appearance  noticed  by  Hippocratesf 
but  to  which  little  attention  has  been  paid.  Lonjon 
thinks  that  in  every  case  of  jaundice  the  velum  palati  shows 
a  deep  and  constant  yellow  colour.  J  And  Pupier  says 
that  the  roof  of  the  mouth  is  the  first  to  show  the  yellow 
colour  and  the  lajst  to  lose  it.§  It  is  true  that  the  roof, 
where  the  bone  is  thinly  covered,  usually  does  show  a 
yellow  tint. 

The  secretion  of  mucous  surfaces  and  those  of  the 
glands  which  open  upon  mucous  surfaces  or  the  skin, 
saving  always  the  notorious  example  of  the  kidneys,  do 
not  as  a  rule  contain  bile  pigment.  The  saliva  is 
colourless.  I  have  often  tested  it  in  cases  of  severe 
jaundice  without  being  able  to  detect  any  reaction  with 
nitric  acid.||  In  like  manner  the  tears,  the  sweat,  and 
the  milk  of  jaundiced  patients  are  as  colourless  as  in 
health.      To  this   statement  there  are  rare  exceptions. 

*  Villeneuve  {Diet,  des  Sciences  vied.  Paris,  1818,  Vol.  xxiii.  p.  405)  says  the  lips 
become  a  deep  yellow,  and  Lonjon  {Gaz.  med.  de  Paris,  1845,  p.  231)  that  the 
inside  of  the  mouth  is  yellow. 

f  Hippocrates,  Dc  morb.  Lib.  ii.  Cap.  xxxviii.  Littre's  ed.  t.  vii.  p.  54. 

I  Lonjon,  loc.  cit.  Decaisne  [Comptcs  rendus  des  Seances  de  VAcademie  des 
Sciences,  1871,  t.  Ixxiii.  p.  i486)  noticed  the  same  appearance  in  an  epidemic  of 
jaundice  at  Paris. 

§  Pupier,  Gaz.  hebd.  1875,  p.  307. 

II  Mosler  {Berliner  klin.  Wochcnschrift,  1866,  p.  173)  could  find  neither  bile  pig- 
ments nor  bile  acids  in  the  saliva  of  the  parotid  gland  from  three  jaundiced  patients. 
Dr.  Samuel  Fenwick,  indeed,  {Lancet,  iSjj,  vol.  ii.  p.  303)  says  that  he  has  examined 
the  saliva  in  a  large  number  of  cases  of  jaundice,  and,  whenever  the  disease  has 
been  recent,  that  he  has  found  the  pigment  on  evaporation.  Nothing  is  said  about 
any  chemical  means  having  been  used  for  the  recognition  of  the  pigment,  so  that 
the  presence  of  biliary  pigment  in  the  specimens  examined  remains  doubtful. 


the  Secretion  of  Glan  d 

The  sweat  is  the  most  common  exception.*  The  Hnen 
near  the  armpits  may  often  be  seen  stained  yellow  as  if 
wetted  with  the  urine.  This  is  certainly  the  most  com- 
mon place  for  the  sweat  to  be  coloured,  although  the 
appearance  of  colour  in  other  parts  has  been  recorded. 
Thus  in  an  old  case  of  Chomel's,  in  a  woman  subject  to 
epilepsy,  jaundice  came  on  ;  a  thick  sweat  broke  out 
during  the  fit,  and  the  linen  with  which  they  wiped  the 
patient  was  tinged  of  a  saffron  colour. "j*  Sir  Henry 
Marsh  says  that  Cheyne  had  met  with  a  patient  whose 
handkerchief  was  stained  yellow  when  she  wiped  her 
face. J  Andral  mentions  a  really  curious  case  in  which 
the  stools  were  white,  but  the  skin  and  conjunctiva 
colourless;  nevertheless  the  urine  was  bilious  and  the 
linen  used  to  wipe  the  sweat  off  the  head  was  coloured 
yellow.  After  death  the  liver  was  found  softened,  not 
fatty ;  the  cystic  and  hepatic  ducts  free  from  bile  and  a 
colourless  serous  fluid  in  the  gall  bladder ;  nothing 
unnatural  was  found  in  the  duodenum. §  Textural 
changes,  like  those  in  the  kidneys,  do  not  appear  in 
the  sweat  glands.  Frerichs  figures  brownish  granules 
within  the  glands,  but  nothing  like  the  great  masses  of 
pigment  seen  in  the  kidney.  || 

There  are  some  early  notices  of  a  change  of  colour 
of  the  saliva  in  jaundice,^  and  one  of  the  best  of  these 
we  owe  to  so  excellent  an  observer  as  John  Huxham. 
A  gentleman  40  years  old,  jaundiced,  took  overnight, 
with  some  other  medicines,  gr.  viii.  of  calomel.  The 
next  day  a  very  green  saliva  poured  out  of  the   man's 

*  Noticed  by  Galen,  De  sanitate  tuenda,  Lib.  iv.  Cap  iv.  Kiihn's  ed.  Lipsije, 
1823,  vol.  vi.  p.  250.     It  is,  however,  only  said  that  the  sweat  is  bitter. 

f  Chomel,  Histoire  de  VAcademie  royale  des  Sciences,  Annee  1737,  Paris,  1740, 
p.  49. 

X  Henry  Marsh,  Dublin  Hospital  Reports,  1822,  Vol.  iii.  p.  269. 

§   Andral,  Cliniqiie  med.  Paris,  1839,  4e  ed.  t.  ii.  p.  374.     Cf.  p.  320. 

II  Frerichs,  Path.-anat.  Atlas  ziir  Klinik  der  Leberkrankheiten,  Tafel  i.  Fig.  6. 

^  Nuck,  Sialographia,  Lugd.  Batav.  1690.  p.  49.  Riedlinus,  Linece  Medicce, 
August.  Vindelic.  Anni  1697.  p.  88. 


262  Presence  of  Bile  Pigment 

mouth,  exactly  like  green  bile,  but' thinner.  This  flow 
of  green  saliva  lasted  40  hours,  and  very  nearly  equalled 
two  quarts  in  amount.  The  green  colour  of  the  saliva 
passed  into  yellow,  which  lasted  another  40  hours  and 
then  the  salivation  disappeared  as  suddenly  as  it  came 
on.  Huxham  does  not  think  it  due  to  the  mercury,  on 
account  of  the  smallness  of  the  dose;  the  patient  had 
before  been  salivated,  apparently  without  mercury,* 
But  the  observer  who  has  paid  the  most  attention  to 
the  saliva,  whether  in  health  or  disease,  is  undoubtedly 
Samuel  Wright ;  and  he  has  published  the  most  com- 
plete account  known  of  the  saliva  in  jaundice.  He 
says  that  in  jaundice,  the  saliva  is  seen  in  two  forms, 
colourless  and  coloured,  and  that  the  coloured  bilious 
saliva  is  of  various  shades,  from  a  golden  yellow  to  a 
-deep  olive  ;  it  is  always  abundant,  and  though  it  some- 
times alternates  with  that  of  other  secretions,  it  rarely 
permanently  diminishes  until  the  patient  be  free  from 
the  jaundiced  tinge.  The  salivary  glands  are  usually 
tinged  and  of  a  dull  red  colour,  but  they  are  not  pain- 
ful and  they  show  no  signs  of  active  inflammation. f 
Wright  thinks  a  discharge  of  bilious  saliva  may  pre- 
cede, accompany,  or  even  hinder,  an  attack  of  jaundice. 
He  gives  three  cases  of  coloured  saliva,  in  all  of  which 
salivation  was  present  ;  and  in  the  two  first  mercury 
was  given  ;  in  the  third  the  treatment  was  by  "  salines 
and  aperients."  The  saliva  tavSted  bitter  to  the  pa- 
tients themselves.  Dr.  Budd  likewise  speaks  of  a  case 
of  jaundice  in  which  salivation  was  caused  by  mercury, 
and  the  saliva  was  deeply  coloured  with  bile. J  Since, 
however,  the  custom  of  giving  mercury  for  jaundice  has 
fallen  out  of  use,  such  cases  seem  to  be  less  common. 
Leyden,  giving  two  grains  of  calomel  every  three  hours, 

*  Huxham,  Phil.  Trans.  1724.  Vol.  xxxiii.  p.  63. 

f  Wright,  Lancet,  1842-43.  Vol.  i.  p.  559. 

J  George  Budd,  On  Diseases  of  the  Liver,  London,  1857.  Third  Ed.  p.  469. 


in  Saliva  and  in  Milk.  263 

caused  a  salivation  ;  and  with  the  saHvation  a  distinct 
yellow  appearance  of  the  saliva.* 

The  records  of  a  bilious  saliva  without  salivation  are 
rare,  a  yellow  appearance  of  the  buccal  mucus  being 
always  excepted. f  There  is,  indeed,  a  case  of  Dr. 
Hilton  Fagge's,  in  which  the  saliva  just  before  death 
had  the  colour  of  bile.  The  patient,  a  woman,  had  for 
six  months  suffered  from  a  macular  syphilide,  and  for 
three  months  from  jaundice  ;  she  denied  having  used 
mercury  ;  but  during  the  10  days  of  her  stay  in  Guy's 
Hospital  she  had  the  ^q  gr.  of  perchloride  of  mercury 
given  three  times  a  day,  and  on  the  day  before  death 
three  grains  of  calomel.  It  does  not  appear  that  there 
was  any  notable  salivation. §  Gubler  also  shortly  men- 
tions a  case  of  syphilis  and  jaundice  in  which  the  saliva 
was  yellow  ;  he  does  not  say  that  the  patient  was  sali- 
vated. § 

The  milk  of  women  suckling  sometimes  contains  bile 
pigment.  This  was  first  proved  by  means  of  chemical 
tests  by  Gorup-Besanez.||  Older  cases  of  a  yellow 
appearance  of  the  milk  in  jaundice  have  likewise  been 
recorded.^  Hervieux  found  quite  lately,  in  an  epi- 
demic jaundice  in  the  Maternite  at  Paris,  that  in  all  the 
women  who  were  suckling,  the  milk  was  coloured  yel- 

*  Leyden,  Beitrdge  zur  Pathologic  des  Icterus.  Berlin,  1866.  p.  208. 

f  Andral,  Clinique  tiled.  Paris,  1839.  46  Edition,  t.  ii.  p.  320. 

i  Hilton  Fagge,  Trans,  of  the  Path.  Soc.  of  London,  1867.  Vol.  xviii.  p.  136. 

§  Gubler,  Gaz.  med.  de  Paris,  1854,  P*  2^5" 

II  Gorup-Besanez,  Arch.f.phys.  Heilkunde,  1849.  Jahrg.  viii.  p.  719. 

II  Peter  Frank,  De  curandis  hominum  morbis,  Vienna,  1821.  Lib.  vi.  pars  iii. 
p.  305.     The  vaginal  secretion  was  likewise  coloured. 

Henry  Marsh,  Dublin  Hospital  Reports,  1822.  Vol.  iii,  p.  263. 

Bright,  Guy's  Hospital  Reports,  1836.  Vol.  i.  p.  623. 

Wunderlich,  Arch.  d.  Heilkunde,  1860.  Jahrg.  i.  p.  35. 

Marsh's,  Bright's,  and  Wunderlich's  cases  are  from  observations  on  the  mam- 
mary gland  after  death.  There  are  some  other  cases  sometimes  set  down  as 
instances  of  bile  being  present  in  the  milk,  which  merely  show  that  the  milk  had 
from  some  cause  or  other  a  bitter  taste.  (01.  Borrichius,  in  Bartholini  Acta  med. 
Hafniensia,  1673.  Vol.  ii.  p.  164.  Obs.  Ixii,  and  Saniml.  atis.  Abh.  1792.  Bd.  xv, 
p.  121.     Note.) 


264  Presence  of  Bile  Pigment 

low.*  Underwood  says  that  he  has  met  with  some 
striking  instances  in  which  women,  suckhng  and  jaun- 
diced, have  communicated  the  disease  to  their  offspring, 
which  has  not  been  cured  until  the  child  was  weaned 
or  the  nurse  recovered. f 

I  have  never  been  so  fortunate  as  to  see  the  milk 
coloured  in  jaundice.  A  patient  of  mine,  suckling,  who 
had  symptoms  of  simple  jaundice,  told  me  that  the  milk 
was  coloured  green.  Yet  on  some  being  pressed  out  of 
the  nipple,  no  colour  was  apparent ;  neither  on  apply- 
ing Gmelin's  test,  could  any  certain  reaction  be  seen  ; 
the  layer  of  milk  above  the  nitric  acid  became  of  a  dirty 
yellow,  markedly  different  from  the  white  of  the  milk, 
but  no  play  of  colours  or  distinct  green  was  seen.  Nor 
did  a  green  colour  develope  in  the  milk  after  it  was  kept 
three  days. 

As  to  the  other  secretions  they  seem  to  be  very  rarely 
coloured.  Heberden  is  commonly  quoted  as  an  au- 
thority for  the  statement  that  the  tears  sometimes  be- 
come yellow  ;  all,  however,  that  he  does  say  is  that  one 
man  assured  him  his  tears  were  tinged  in  a  jaundice. J 
Some  French  writers  speak  of  the  tears  in  the  jaundice 
of  the  new-born  being  coloured  ;  but  I  think  this  must 
be  a  mistake,  the  pus  of  an  ophthalmia  being  coloured 
yellow  and  thus  thought  to  be  tears. § 

Sander  says  that  the  nurse  attending  one  of  his  cases 
which  died  of  acute  yellow  atrophy,  reported  that  the 
tears  were  yellow.  ||  This  suffers  the  same  want  of 
proof  as  Heberden's  case,  as  the  doctor  himself  did  not 
see  the  tears. 

The  mucus  of  the  nose  has  been  seen  to  be  yellow  by 

*  Hervieux,  Union  mid.  1872.  t.  xiii.  p.  610. 

f  Underwood,  A  Treatise  on   the  Diseases  of  Children, 'LonA.  1805.  Fifth  edit, 
vol.  i.  p.  27. 

J  Heberden,  Commentaries,  Lond.  1806.  3rd  ed.  p.  247. 

§  Billard,  Traite  des  maladies  des  enfans  nonveau-nis,  Paris,  1828.  p.  646. 

II  Sander,  Deutsche  Klinik,  i860.  Bd.  xii.  p.  33. 


in  the  Mucous  Secretions.  265 

one  or  two  observers  ;*  Joseph  Frank  says  he  has  seen 
the  secretion  of  the  ears  altogether  suppressed  in  jaun- 
dice.f  It  is  hkewise  asserted  that  the  vaginal  mucus 
is  sometimes  coloured. J  Bouisson  says  he  has  found 
the  semen  in  the  vesiculcB  seminales  manifestly  yellow. § 

The  fluids  poured  into  the  intestinal  tract  are  like- 
wise devoid  of  colour  in  jaundice  ;  otherwise  the  faeces 
themselves  would  be  coloured.  I  am  not  acquainted 
with  any  well  authenticated  case  in  which  these  fluids 
were  coloured ;  indeed  it  would  be  hard  to  prove 
the  presence  of  bile  pigment  in  them,  apart  from  the 
faeces. II  Osborne  speaks  of  colourless  faeces  floating 
in  a  bilious  fluid, ^j  but  this  seems  to  me  best  explained 
by  supposing  an  admixture  of  urine. 

Although  the  mucous  secretions  remain  uncoloured 
in  jaundice  while  the  mucous  membranes  and  glands 
remain  healthy,  yet  the  secretions  may  become  coloured 
in  disease.  This  has  been  already  noticed  in  the  case 
of  the  saliva.  Simple  catarrh  does  not  seem  to  beget 
much  change  ;  but  the  croupous  exudations  are  very 
liable  to  be  coloured  in  jaundice.  For  example,  in 
simple  catarrh  of  the  bronchial  tubes,  the  mucus  is 
rarely  coloured,  although  I  have  met  with  such  an  in- 
stance in  one  case  ;  yet  in  pneumonia  complicated  with 
jaundice,  where  a  croupous  exudation  takes  place,  the 
sputa  are  very  commonly  coloured. 

*  Kercksig,  Hufeland's  jfournal,  1799.  Bd.  vii.  Stiick  iii.  p.  98.  There  is  also  an 
old  case  by  Riedlinus,  LinecB  med.  anni  1697.  August.  Vindel.  p.  88. 

f  Joseph  Frank,  op.  cit.  p.  282. 

+  Peter  Frank,  De  curand.  horn.  morb.  Viennae,  1821.  Lib.  vi.  Pars  iii.  p.  305. 

Reclus,  Gaz.  des  Hop.  1872.  p.  259. 

Stokes,  Lotid.  Med.  and  Stirg.  yonrnal,  1834.  vol.  v.  p.  199. 

§  Bouisson,  De  la  bile,  Montpellier,  1843.  p.  151.  A  similar  instance  is  quoted 
by  Joseph  Frank  {op.  cit.  p.  281.)  from  Petermann  {Obs.  Med.  Dec.  i.  No.  g.) 

II  Bouisson  {de  la  Bile,  Montp.  1843,  p.  150)  says  that  Voigtel  {Handb.  d.  path. 
Anat.  Halle,  1804,  Bd.  i.  p.  552)  records  a  case  in  which  the  pancreatic  fluid  was 
yellow  in  jaundice.  What  Voigtel  does  say  is  that  a  yellow  fluid  was  found  in 
the  pancreas  of"  a  jaundiced  person. 

%  Osborne,  Dublin  Quarterly  jfotirnal,  1853,  vol.  xv.  p.  106. 


266  Extra-  VasciUar  Tissues  not  coloured. 

The  fluid  exudations  into  the  serous  cavities  are 
among  the  first  to  show  the  presence  of  bile  pigment. 

The  extra-vascular  tissues  are  not  coloured  in  jaun- 
dice. There  are  old  stories  quoted  of  the  hairs  some- 
times changing  colour  ;  which  on  examination  do  not 
bear  out  the  purpose  for  which  they  are  brought 
forward :  the  case  quoted  by  Schenck  suggests  chloro- 
sis rather  than  jaundice  ;*  and  Riedlinus'  is  simply 
that  a  jaundiced  woman  told  him  that  whenever  she 
pulled  out  a  hair,  a  yellow  drop  appeared  at  the  spot 
whence  the  hair  came  out.f  Stokes,  however,  tells  us 
that  one  of  his  friends  considered  that  the  hairs  were 
unquestionably  coloured  in  some  cases  of  jaundice.  It 
does  not  seem  that  Stokes  had  ever  seen  such  cases.  J 
Neither  have  I. 

Huxham's  statement  that  the  teeth  were  coloured 
green  for  a  fortnight  after  convalescence  in  his  case  of 
bilious  saliva§  is  confirmed  by  Wright,  who  says  that 
in  like  cases  he  has  seen  the  teeth  coloured  permanently 
yellow,  green,  brown,  or  black  according  to  the  amount 
of  bile  present  in  the  saliva.  ||  Thomas  Bell  says  he 
has  seen  more  than  one  example  of  the  injection  of  a 
tooth  with  bile  in  cases  of  jaundice.^  It  would  seem 
from  Bell's  statement  that  only  one  tooth  was  coloured 
among  many.  The  rule  in  jaundice  is  that  the  teeth 
look  uncommonly  white  from  contrast  to  the  surround- 
ing coloured  tissue,  as  the  teeth  of  a  negro  do. 

There  is  a  curious  case  mentioned  by  Bleicher,  of  a 
man  aged  40  who  on  the  8th  day  of  a  jaundice  with 
fever,  passed  blue  urine  ;    and   at  the   same  time  the 

*  Schenck,  Obs.  med.  Lib.  iii.  de  ictero,  Obs.  i.  Lugduni,  1644,  p.  405.  Quoted 
from  Cornelius  Gemma,  Comoscrit.  lib.  i.  cap.  7. 

f  Riedlinus,  LinecE  med.  Anni  1697,  August.  Vindel.  p.  88. 

\  Stokes,  Loud.  Med.  and  Surg,  journal,  1834,  vol.  v.  p.  igg. 

§  Huxham,  Phil.  Trans.  1724,  vol.  xxxiii.  p.  64. 

II  Wright,  Lancet,  1842-43,  vol.  i.  p.  562. 

IT  Thomas  Bell,  John  Hunttr's.  Works,  Palmer's  ed.  London,  1835,  vol.  ii.  p.  19, 
note. 


Drowsiness  of  Jaundice.  267 

lips,  tongue,  and  teeth,  became  blue.  Eight  days  after 
he  was  cured.* 

Pain  is  not  a  compHcation  of  jaundice.  Jaundice 
caused  solely  by  the  pressure  of  a  tumour  upon  the 
hepatic  ducts,  or  by  a  plug  of  mucus  within  them,  is  not 
accompanied  by  any  pain  due  to  the  jaundice  ;  if  pain 
be  present  it  is  due  to  some  other  complication  of  the 
disease".  It  is,  however,  otherwise  when  the  jaundice  is 
due  to  the  passage  of  a  rough  angular  gall  stone  down 
the  ducts  ;  the  friction  and  forcible  dilatation  of  the 
ducts  sometimes  cause  agony  so  great  that  it  is  needful 
to  give  the  patient  chloroform  to  remove  the  pain. 

Pouzol,  speaking  of  the  slight  troubles  and  absence 
of  pain  which  in  general  accompany  jaundice,  says 
that  he  has  noticed  a  headache  sometimes  attend 
this  disease  :  the  headache  is  frontal  or  general,  some- 
times lancinating,  sometimes  giving  a  feehng  of  weight,  j" 
This  is  probably  bilious  in  origin. 

Patients  with  jaundice  appear  to  me  to  be  drowsier 
than  others.  They  often  sleep  much  during  the  day. 
Sleeplessness,  unless  due  to  the  itching,  is  not  at  all  a 
common  symptom,  although  spoken  of  as  one. J 

Heberden  speaks  of  hiccup  being  seen  in  jaundice, 
but  without  denoting  any  present  or  future  mischief.  § 

Symptoms  of  disordered  digestion  are  seen  in  cases 
of  jaundice  complicated  with  signs  of  gastric  catarrh  ; 
that  is,  a  large  proportion  of  cases.  But  in  many 
cases  of  chronic  jaundice,  digestion  seems  to  suffer 
but  little.  The  appetite  is  good  and  the  tongue  re- 
mains clean.  Frerichs  states  that  the  patients  suffer 
from  much  flatulence,  due  to  the  want  of  bile  in  the 
intestine.il      Curiously  enough,    Hippocrates   says  pre- 

*  Bleicher,  Schmidt's  yahrbb.  1839,  Bd.  xxi.  p.  48. 

f  Pouzol,  Essai  sur  Victere,  Paris,  1872,  p.  78.  Portal  {Maladies  dtifoie,  Paris, 
1813,  p.  133)  says  shortly  that  heat  and  weight  of  the  head  are  often  seen  in 
jaundice.  J  Pouzol,  loc.  cit. 

§  Heberden,  Commentaries,  Lond.  1806.  Third  ed.  p.  246. 

II  Frerichs,  op.  cit.  Bd.  i.  p.  118. 


268  Presence  of  Bile  in 

cisely  the  reverse,  that  the  jaundiced  are  not  at  all 
flatulent  ;*  and  in  my  experience  of  chronic  jaundice 
it  has  not  been  at  all  a  prominent  symptom.  There 
seems  to  be  a  dislike  to  fat.  Those  who  in  health  have 
eaten  and  liked  fat,  when  jaundiced,  refuse  it.  Budd 
describes  a  patient  who  had,  at  times,  a  voracious 
appetite,  with  a  craving  for  oysters  and  small  shell-fish, 
which  even  in  large  quantities,  never  disagreed. f 

The  blood  early  suffers  in  jaundice.  Saunders  showed 
that,  within  two  hours  after  ligature  of  the  bile  duct,  the 
blood  gave  evidence  of  the  presence  of  bile  pigment.  J 
I  have  repeated  this  experiment,  following  Saunders' 
directions  exactly,  but  without  attaining  his  results. J 
Frerichs  in  like  manner,  could  only  detect  bile  pigment 
in  the  blood  at  the  end  of  48  hours  after  the  ligature  of 
the  ducts. §  I  quite  agree,  however,  with  his  statement 
that  bile  pigment  may  be  found  after  death  in  the  serous 
effusions  of  the  chest  or  belly  in  cases  where  none  can 
be  detected  in  the  urine,  or  any  change  of  colour  seen 
in  the  skin.  I  have  several  times  verified  this  state- 
ment, taking  care  to  use  only  the  fluids  from  the  chest, 
as  it  may  be  objected  to  those  from  the  belly  that  the 
bile  in  the  gall  bladder  may  have  transuded  after  death. 

It  is  granted  by  all  that  the  bile  pigments  exist  in  the 
blood  in  jaundice. ||  The  same  cannot  be  said  of  the 
bile   acids.      For  many   years    a  fruitless   search   was 


*  Hippocrates,  Aphorisms,  Section  v.  §  72.  Littre's  ed.  t.  iv.  p.  562.  Oi  iKri^iu'SiK 
el  tayu  ri  -Trviuf/.a.ruii'is  iiirii. 

f  Budd,0«  Diseases  of  the  Liver,  London,  1857,  third  ed.  p.  2ig. 

+  Saunders,  A  Treatise  on  the  Structure,  Economy,  and  Diseases  of  the  Liver, 
London,  1803,  3rd  ed.  p.  in. 

+  Wickham  Legg,  St.  Bartholomew's  Hospital  Reports,  1873,  vol.  ix.  p.  176. 

§  Frerichs,  op.  cit.  Bd.  i.  p.  99. 

II  See  hecanu,  Transactions  med.  iS^i,  t.  VI.  p.  113,  note,  for  the  bibliography 
of  the  older  researches  into  the  presence  of  the  colouring  matter  of  the  bile  in  the 
blood.  I  have  looked  through  these  references,  but  the  authors  do  not  communicate 
any  important  results.  Kane  {Dublin  journal,  1833,  vol.  ii.  p.  346)  confirms 
Lecanu's  statements. 


the  Blood  of  Jaundice.  269 

made  for  them,  only  one  chemist*  since  Pettenkofer's 
discovery,  and  that  not  in  cases  of  disease  of  the  Hver, 
being  able  to  find  their  peculiar  reaction  in  the  blood. 
In  1858  came  Hoppe-Seyler's  discovery  of  the  bile  acids 
in  the  urinef  and  Kiihne  soon  after  found  them  in  the 
blood  of  jaundiced  dogs,  even  so  soon  as  24  hours  after 
complete  occlusion  to  the  ducts. ^ 

Huppert  found  them  in  the  blood  of  a  rabbit  who 
lived  only  six  and  a  half  hours  after  the  bile  ducts  were 
tied,  and  in  the  blood  of  a  cat  who  lived  more  than 
sixteen  hours  after. §  Also  in  the  blood  of  a  man  who 
died  of  acute  yellow  atrophy.  But  Ernst  Bischoff 
could  not  find  them  in  the  blood,  muscles,  brain,  or 
cerebro-spinal  fluid  of  a  patient  who  died  with  intense 
jaundice  from  cancer  of  the  liver. || 

When  it  was  the  custom  to  make  analyses  of  the 
blood  in  mass,  analyses  to  which  little  regard  is  now 
paid,  several  examinations  of  the  blood  from  jaundiced 
persons  were  made.  Lecanu^I  and  Simon**  found  the 
amount  of  colouring  matter  of  the  corpuscles  decreased, 
while  Denisft  found  the  globules  natural  in  amount, 
but  the  albumen  decreased.  Gorup-BesanezJJ  found 
an  increase  of  the  water,  and  decrease  of  the  blood- 
corpuscles  ;  and,  at  the  same  time  no  increase  of 
fatty  matters,  and  no  cholestearin.  The  absence  of 
any  increase  of  fat   or   cholestearin  was  noticed    also 

*  C.  G.  Lehmann,  Lehrb.  d,  phys.  Chem.  Leipzig,  1853,  ate  Aufl.  Bd.  i.  p.  122. 
Jac.  Moleschott  (Z eitschrift  f.  rat.  Med.  1847,  ^^-  ^-  P-  3^7)  thought  he  detected 
bilin,  i.e.  the  bile  acids  in  the  blood  in  a  case  of"  hepatitis." 

t  For  history  of  this,  see  the  section  on  the  urine. 

X  Kuhne,  Arch.  f.  path.  Anat.  1858,  Bd.  xiv,  p.  347. 

§  H.  Huppert,  Arch.  d.  Heilk.  1864.  Jahrg.  v.  p.  253. 

II  Ernst  Bischoff,  Zeitschriftf.  rat.  Med.  1864,  iii.  Reihe,  Bd.  xxi.  p.  142. 

%  Lecanu,  Trans,  med.  1831,  t.  vi.  p.  109.  The  blood  which  he  examined  did 
not  clot  till  long  after  it  had  cooled. 

**  Simon,  Animal  Chemistry,  Day's  Trans.  1845,  vol.  i.  p.  330. 

f  f  Denis,  Essai  sur  V application  de  la  Cheinie  d  V etude  physiologique  du  Sang, 
Paris  1838,  p.  309. 

11  Gorup-Besanez,  Arch.f.  phys.  Heilk,  1849,  Bd.  viii.  p.  530. 


270  State  of  the  Blood  in  Jaundice. 

by  Kane*  and  Simonf.  On  the  other  hand  Becquerel 
and  Rodier  found  an  increase  in  the  fatty  matters  and 
cholestearin  ]%  Frerichs,  a  large  increase  in  the  fatty 
matters,  which  were  rich  in  cholestearin,  and  which 
rose  sometimes  to  4  or  5  per  cent.  Leucin  was  also 
found  in  the  blood. § 

Dr.  Samuel  West  found,  "in  a  case  of  severe  jaun- 
dice, probably  depending  on  gall  stones,  the  patient  being 
in  a  state  of  the  most  extreme  anasmia,  and  so  weak 
that  the  least  exertion  caused  fainting,"  that  the  blood 
showed  the  following  characters :  "  The  cells  were 
considerably  diminished  in  number,  and  the  blood  very 
watery.  The  red  cells  did  not  form  rouleaux,  were 
much  diminished  in  size,  hardly  half  as  large  as  a 
healthy  red  cell,  most  irregular  in  shape,  and  deeply 
coloured,  resembling  the  bodies  described  by  Lebert 
as  tubercle  corpuscles.  The  white  cells  were  in  rela- 
tive excess.  In  this  one  particular  only  did  the  blood 
in  the  case  differ  from  that  described  in  idiopathic  or 
pernicious  anaemia.  The  patient,  however,  recovered, 
and  with  his  improvement,  his  blood  gradually  returned 
to  its  normal  condition;  and  on  his  leaving  the  Hospital 
this  note  is  recorded  :  Red  blood  cells  nearly  natural 
again  ;  here  and  there  one  still  misshapen.  They  form 
rouleaux  ;  the  white  are  no  longer  in  excess. "|| 

Budd,  though  he  seems  to  have  made  no  analyses, 
says  that,  after  jaundice  has  lasted  some  time,  the  glob- 
ules of  the  blood  are  always  less  in  proportion  than  in 
health.  This  probably  results,  not  so  much  from  the 
mere  presence  of  the  principles  of  the  bile  in  the  blood 
as  from  a  diminution  of  those  reparative  changes  which 

*  Kane,  Dublin  Journal,  1833,  vol.  ii.  p.  346. 
f  Simon,  loc  cit. 

X  Becquerel  and  Rodier,  Recherchcs  sur  la  composition  du  Sang,   Paris,    1844. 
p.  106. 

§  Frerichs,  op.  cit.  Bd.  i.  p.  103. 

II  Samuel  West,  St.  Bartholomew's  Hospital  Reports,  1877,  vol.  xiii.  p.  218. 


The  F(Bces  in  Jaundice.  271 

the  blood  naturally  undergoes  in  its  passage  through 
the  liver,  and  to  the  impaired  digestion  which  results 
from  the  absence  of  bile  in  the  bowel.*  Leyden  seems 
to  incline  to  believe  that  the  poverty  of  the  blood  is  due 
to  the  action  of  the  bile  acids  upon  the  corpuscles. f 
For  my  own  part,  I  feel  disposed  to  agree  with  Budd  and 
attribute  the  state  of  the  blood  to  the  impaired  action 
of  the  liver  and  the  impaired  nutrition  rather  than  to  the 
solvent  action  of  the  bile  acids  upon  the  corpuscles. 

The  fceces  in  jaundice  are  often  entirely  wanting  in 
colour.^  They  have  a  grey  or  clay  coloured  appear- 
ance, and  are  less  consistent  than  the  stools  seem  in 
health.  Frerichs,  however,  says  that  the  stools  are 
firmer  and  more  consistent. §'  To  this  statement,  I 
fear,  I  cannot  assent ;  or  to  that,  that  constipation  is 
the  rule.  In  simple  jaundice,  which  is,  I  suppose,  the 
most  common  of  all  kinds  of  jaundice,  diarrhoea  is  very 
often  seen.  In  chronic  jaundice,  diarrhoea  is  less  com- 
mon. In  this  statement  I  am  supported  by  no  less 
profound  an  observer  than  Heberden  ;  who,  granting 
that  costiveness  might  be  looked  for  in  jaundice,  as  the 
irritation  from  the  bile  is  wanting,  says  that  in  fact 
icteric  persons  are  often  disposed  to  have  a  purging. 
He  looks  upon  the  diarrhoea  as  a  help  to  distinguish 
jaundice  from  ileus. || 

Sometimes  the  faeces  are  particoloured ;  some  part 
being  more  deeply  stained  with  bile  than  the  other ; 
or  even  one  part  free  from  bile  altogether,  while  the 

*  Budd,  On  Diseases  of  the  Liver,  London,  1857,  3rd  ed.  p.  468. 

f  Leyden,  Beitrdge  ziir  Pathologie  des  Icterus,  Berlin,  1866,  p.  117. 

X  Hippocrates  describes  the  stools  as  yellow-white  and  stinking.  {De  morb.  int. 
Cap.  XXXV.  Littre's  ed.  t.  vii.  p.  252.)  Aretasus  says  that  their  want  of  colour  is  due  to 
absence  of  bile.  {On  the  Causes  and  Symptoms  of  Chronic  Diseases,  Book  i.  Chapt. 
XV.  Adams'  transl.  p.  324.) 

§  Frerichs,  op.  cit.  Bd.  i.  p.  119. 

II  Heberden,  Commentaries,  Lond.  1806.  Third  ed.  p.  246.  The  same  opinion 
is  expressed  by  Powell.  {Observations  on  the  Bile  and  its  diseases,  London,  1800, 
p.  85. 


272  The  FcBces  in  Jaundice. 

other  is  coloured.  Graves  explains  this  appearance  by 
supposing  that  the  liver  secretes  bile  during  a  certain 
part  of  the  digestive  process,  then  stops,  and  then 
secretes  again.*  It  is  rare  in  jaundice  for  the  fasces  to 
be  unchanged  in  colour,  or  to  show  more  staining  with 
bile  than  natural.  This  last  has  given  rise  to  theories  of 
polycholia,  or  an  excess  of  bile,  as  a  cause  of  jaundice  ; 
and  is  one  of  the  points  relied  upon  by  the  defenders  of 
the  theory  of  hsematogenous  jaundice.  Doubtless  the 
appearance  of  highly  coloured  faeces  is  sometimes  hard 
to  explain  upon  the  theory  of  an  obstruction  to  the  duct 
if  the  admixture  of  foreign  colouring  matters,  such  as 
blood  or  drugs,  can  be  disproved.  Still  it  is  well  to  keep 
in  mind  the  facts  disclosed  by  morbid  anatomy  :  some 
of  the  small  ducts  may  be  obstructed  high  up  in  the 
liver,  while  the  large  ducts  and  branches  leading  into 
them  are  quite  free  ;  also  the  small  amount  of  colouring 
matter  that  need  be  in  the  blood  to  bring  about  the 
appearance  of  jaundice. 

If  the  faeces  be  colourless,  there  can  be  little  doubt 
that  no  bile  enters  the  intestine  ;  in  other  words,  that 
the  obstruction  of  the  bile  duct  is  complete.  But  the 
contrary  does  not  hold  good.  The  faeces  may  owe  their 
colour  to  other  sources  than  the  bile  ;  as  the  adminis- 
tration of  drugs,  like  charcoal,  bismuth,  or  iron.  Like- 
wise the  appearance  of  haemorrhages  into  the  intestinal 
tract  in  jaundice  is  far  from  uncommon,  and  blood 
mixed  with  the  stools  may  readily  give  the  deceptive 
appearance  of  a  dark  or  brown  colour  to  the  fasces.  I 
cannot,  however,  agree  with  Osborne  that  it  is  possible 
that  the  secretions  from  the  bowels  may  be  coloured 
while  the  faeces  are  white.  He  says  that  the  faeces  in 
jaundice  may  be  seen  to  be  of  a  white  colour  like  putty, 
surrounded  by  a  green  or  yellow  liquid. f    This  seems  to 

*  Graves,  Clinical  Lectures  on  the  Practice  of  Medicine,  Dublin,  1864,  p.  342. 
Reprint  ot  second  ed.  edited  by  Neligan. 

f  Osborne,  Dublin  Quarterly  Journal,  1853,  vol.  xv.  p.  106. 


The  FcBces  in  Jaundice.  273 

me  to  be  due  possibly  to  some  error  of  observation. 
The  faeces  may  not  unfrequently  be  seen  surrounded  by 
a  coloured  liquid,  but  this  is  in  cases  where  the  bilious 
urine  has  been  suffered  to  mix  with  the  uncoloured 
stools,  and  thus  a  deceptive  appearance  caused. 

The  faeces  in  jaundice  do  not  seem  to  have  been 
examined  with  much  attention  by  the  chemists.*  Dr. 
Austin  Flint,  the  younger,  has  found  that  they  contain  no 
stercorin,"f*  a  substance,  which  he  says,  is  derived  from 
the  decomposition  of  cholestearin,  and  which  always 
appears  in  natural  fasces.  Dr.  Flint  thinks  that  no 
cholestearin  is  found  in  natural  fasces.  Hoppe-Seyler 
commenting  on  Dr.  Flint's  researches  says  that  ster- 
corin  is  nothing  more  than  an  impure  cholestearin ; 
cholestearin  itself  being  abundantly  found  in  the  faeces 
of  mammalia,  including  man.  J  A  large  amount  of  fat 
was  also  found  by  Dr.  Flint  in  the  faeces  of  jaundice  : 
Farines,  in  an  old  analysis,  found  the  greater  part  of 
the  fasces  in  jaundice  to  be  formed  of  a  fatty  matter, 
soluble  in  cether.§  A  like  result  was  attained  by  Trom- 
mer,  who  analysed  the  faeces  of  one  medical  student  who 
was  jaundiced,  and  compared  the  results  with  those 
obtained  from  the  faeces  of  another  medical  student,  who 
was  healthy,  but  ate  the  same  food.  Far  more  fat  was 
found  in  the  faeces  of  the  former  than  of  the  latter.  || 
Jaundiced  persons,  it  is  well  known,  dislike  fat. 

The  Urine.     The  urine  very  early  shows  changes  in 
jaundice.      It   becomes   highly   coloured.^     Linen    or 

*  See  Hoppe-Seyler,  Phys.  Chemie,  Berlin,  1878,  p.  358. 

f  Austin  Flint,  Recherches  exp.  sur  une  nouvelle  fonctioii  du  foie,  Paris,  1868, 
p,  loi ;  also  in  American  journal  of  the  Medical  Sciences,  1862,  vol.  xliv.  pp.  358 
and  364. 

J  Hoppe-Seyler,  Virchow's  jfahresberichff.  1868,  Bd.  i.  p.  97. 

§  Farines,  in  Orfila,  Elcm.  de  chimie  appliqnee  d,  la  med.  et  aux  arts,  Paris,  1836, 
t.  iii.  (Quoted  by  Bouisson,  de  la  Bile,  Montpellier,  1843,  p.  151.) 

II  Trommer,  reported  by  F.  von  Niemeyer,  Text  Book  of  Practical  Medicine, 
trans,  by  Humphreys  and  Hackley,  New  York,  1870,  Vol.  i.  p.  679. 

IT  The  change  in  colour  vi'as  noticed  by  Hippocrates  {De  aff.  int.  Cap.  xxxv. 
Littre's  ed.  t.  vii.  p.  252  ct  seqq.) 

T 


274  ^^^^  Urine  in  Jaundice. 

white  paper  dipped  into  it  is  stained  yellow.  This  is 
an  appearance  often  noticed  by  the  patients  themselves. 
The  froth  on  the  surface  shows  a  yellow  look  and  is 
long  in  disappearing. 

The  colour  may  be  scarcely  darker  than  natural,  and 
need  a  chemical  test  to  show  the  presence  of  bile :  or 
the  urine  may  be  almost  as  dark  as  porter,  of  a  green 
brown,  or  brown  black.  The  reaction  is  acid,  and  the 
specific  gravity  is  not  low,  seldom  falling  below  loio.* 
The  urine  is  commonly  clear  ;  but  may  sometimes  be 
turbid  owing  to  the  presence  of  urates,  apparently  not 
dependent  upon  the  temperature  of  the  patient. 

The  quantity  of  urine  passed  in  the  24  hours  in  jaundice 
is  subject  to  considerable  variations.  Becquerel  found 
in  three  cases  in  which  he  carefully  noted  the  appear- 
ances of  the  urine  that  in  the  first,  a  man,  the  amount 
in  24  hours  was  1419.C.C. ;  in  the  second,  a  man 
jaundiced  after  a  violent  dispute,  it  was  634. C.C.  and 
in  a  third,  a  pregnant  woman,  it  was  640.C.C.t  The 
observations,  however,  were  only  made  on  one  day,  and 
are  therefore  less  valuable  than  those  which  follow  and 
which  were  made  in  succession.  Leyden  found  in  one 
of  his  cases  that  the  urine  was  increased  in  quantity 
whil6  the  temperature  was  normal,  but  sank  in  amount 
during  a  paroxysm  of  fever.:]:  A.  Vogel  found  in  his  case 
of  jaundice  lasting  for  many  months,  and  due  to  cancer 
of  the  liver,  that  the  amount  of  the  urine  varied  from 
1350. C.C.  to  2000.C.C.§  Kolliker  and  Miiller  in  their 
observations  on  a  woman  of  25,  suffering  from  simple 
jaundice  found  that  the  mean  amount  of  the  urine  dur- 

*  Gorup-Besanez  {Arch.  f.  phys.  Hcilkunde,  1849,  Jahrg.  viii.  p.  713)  says  that 
the  specific  gravity  of  the  urine  of  jaundice  is  commonly  high,  about  1031. 

f  Becquerel,  Semciotique  des  Uyiiies,  Paris,  1841,  pp.  413  and  393. 

J  Leyden,  Bcitrdgc  zur  Path,  dcs  Icterus,  Berlin,  1866,  p.  205.  He  likewise 
gives  cases  of  increased  or  abundant  flow  of  urine  at  pp.  114  and  184,  although  in 
the  former  of  these  two  the  temperature  was  high. 

§  A.  Vogel,  Zeitschriftf.  rat.  Med.  1854,  Bd,  iv.  Cneue  Folge)  p.  391. 


Amount  of  Urine  passed.  275 

ing  the  jaundice  was  1670. C.C;  during  the  convales- 
cence 1401.C.C.  ;  when  quite  well  1370. C.C*  So  that 
in  this  case  there  seems  some  evidence  that  the  amount 
of  urine  passed  was  really  increased  in  amount. 

Julius  Jacobs  found  the  amount  in  three  cases  to  be 
24og.C.C.  1638. C.C.  and  i332.C.C.t 

In  four  cases  examined  by  Valmont  the  amount  was 
found  rarely  to  rise  above  1000  C.C.  One  of  these  was 
believed  to  be  a  case  of  cancer  of  the  liver;  in  the  other 
three,  cirrhosis  was  diagnosticated;  and  in  two,  verified 
after  death. J 

I  have  measured  the  amount  of  urine  passed  in  the 
24.  hours  in  ten  cases  of  jaundice  due  to  various  causes. 
The  highest  mean  was  in  a  case  of  complete  obstruc- 
tion to  the  ducts  by  a  hydatid  cyst,  and  equalled  2790 
C.C.  in  the  twenty-four  hours.  The  lowest  mean  was  in 
a  case  of  cancer  of  the  pancreas  and  liver  and  equalled 
570.  C.C.  In  two  other  cases  of  jaundice  due  to  the 
same  cause  the  mean  were  1971.  and  1120.  C.C.  In 
the  remaining  six  cases  the  means  of  the  urine  passed 
were  iioo,  1355,  1433,  1481,  1788,  and  2234.  C.C. 
amounts  not  above  or  below  the  standard  of  health§ 

In  some  cases  of  jaundice  it  has  been  noticed  that, 
as  the  patient  was  dying,  the  amount  of  urine  passed 
become  very  small,  or  indeed  sank  almost  to  nothing. 
Such   a  case  has  been  noticed  by  Devay  in  which  the 

*  Kolliker  und  Miiller,  Verhandlungen  der  phys,  med.  G esellschaft  in  Wi'irzburg, 
1856,  Bd.  vi.  p.  497. 

f  Julius  Jacobs,  Arch.  f.  path.  Aiiai.  1877,  Bd.  Ixix.  p.  487. 

J  Valmont,  Etude  stir  les  causes  des  variations  de  Viivee  dans  quelques  maladies 
du  foic,  These  de  Paris,  1879,  p.  36  et  seqq.  See  also  Vulpian,  CUnique  med.  de 
I'Hopital  de  la  Charite,  Paris,  1879,  p.  253, 

§  Wickham  Legg,  Med.  Chir.  Trans.  1876,  Vol.  lix.  p.  149.  Dogs,  whose  bile 
ducts  have  been  tied,  pass  a  greatly  increased  quantity  of  urine.  Tiedemann  and 
Gmelin  (Recherches  experimentales  snr  la  digestion,  Paris,  1827,  Partie  ii.  p.  47)  also 
noted  that  the  urine  was  abundant.  Feltz  and  Ritter  found  that  after  the  injection  of 
bilirubin  into  the  veins,  the  amount  of  urine  was  much  increased.  (Robin's  your- 
nal  de  VAnat.  et  de  la  Phys.  1875,  t.  xi.  p.  155. 


O  2 


276  Sugar  rarely  present 

urine  was  suppressed  three  days  before  death  after  a  7. 
years'  jaundice  from  gall  stones,* 

Albumen  is  rarely  absent  from  jaundiced  urine.  The 
am.ount  is  indeed  small,  and  some  care  is  needed  to 
detect  it.  No  cloudiness  is  given  by  heat,  as  a  rule  ; 
but  opalescence,  however,  appears  on  dropping  a  little 
nitric  acid  into  the  boiling  urine.  I  look  upon  this  as 
evidence  of  the  presence  of  albumen  in  the  urine.  No 
white  ring  is  commonly  formed  where  a  layer  of  nitric 
acid  touches  the  urine. 

According  to  Kiihne,  the  cause  of  the  presence  of  this 
small  quantity  of  albumen  in  jaundiced  urine  would  be 
due  to  the  action  of  the  bile  acids  upon  the  red  cor- 
puscles.f  It  is  well  known  that  the  red  corpuscles, 
wherever  they  come  in  contact  with  the  bile  acids,  are 
dissolved.  Free  haemoglobin  thus  becomes  present  in 
the  plasma  of  the  blood,  and  is  thrown  out  by  the 
kidneys.  The  bile  acids  must  be  present  in  but  small 
quantity  in  the  blood,  or  a  much  larger  amount  of 
albumen  would  be  thrown  out  by  the  kidneys. 

Sugar  is  not  often  met  with  in  jaundiced  urine.  In- 
deed though  I  have  carefully  looked  for  it  in  nearly 
all  the  cases  which  I  have  examined,  I  have  never 
met  with  it.  The  test  which  I  have  used  has  been 
Trommer's.  On  theoretical  grounds  the  appearance 
of  sugar  should  be  rare,  as  one  important  form  of  dia- 
betes does  seem  to  arise  from  the  liver.  I  have  shown 
that  after  ligature  of  the  bile  duct  glycogen  disappears 
in  the  liver,  and  that  when  the  fourth  ventricle  is  irri- 
tated under  the  same  circumstances,  no  sugar  appears 
in  the  urine.  J  So  in  jaundice  if  the  obstruction  to  the 
ducts  be  complete,  no  sugar  from  the  liver  should 
appear  in  the  urine.      There  are,  however,  a  few  cases 

*  Devay,  Gaz.  mid.  dc  Paris,  1843,  p.  263,  Of.  Frerichs,  op.  cit.  Bd.  i.  p.  147. 
f  Kiihne,  Lehrb.  d.  phys.  Chemie,  Leipzig,  1868,  p.  545. 

X  Wickham  Legg,  St.  Bartholomew'' s  Hospital  Reports,   1873,  Vol.  ix.   p.   161, 
and  Arch./,  exp.  Path.  1874,  Bd.  ii.  p.  384. 


in  the  Urine  of  Jaundice.  277 

in  which  sugar  has  appeared  in  the  urine  of  jaundice. 
In  Golowin's  case,  a  dog  was  artificially  jaundiced,  and 
each  time  that  milk  was  given  to  the  animal,  sugar 
appeared  in  the  urine.* 

Valmont  has,  however,  given  150  or  200  grammes  of 
sirop  de  glucose  to  patients  suffering  from  jaundice,  and 
not  been  able  to  detect  any  sugar  in  the  urine  passed 
afterwards. f  In  some  cases  of  an  advanced  cachexia,  he 
says  that  he  found  the  sugar  again,  but  with  large  doses 
it  is  possible  to  cause  glycosuria  even  in  healthy  people. 

There  is  an  important  case  of  diabetes  recorded  by 
Dr.  Bright,  in  his  paper  on  diseases  of  the  pancreas. 
A  man,  49  years  of  age,  first  felt  symptoms  of  diabetes 
in  the  month  of  March.  In  the  beginning  of  September 
he  began  to  be  jaundiced  ;  and  at  the  end  of  December, 
the  sugar  had  disappeared  from  the  urine.  The  man 
died  on  March  ist,  and  the  common  duct  was  found 
to  end  in  a  ctil  de  sac  in  the  diseased  substance  of  the 
pancreas,  complete  obstruction  having  taken  place. J 
The  theory  of  this  case  would  be  that  the  gradual 
obstruction  of  the  ducts  caused  the  liver  to  cease  its 
glycogenetic  function,  and  the  diabetes  also  to  end : 
while  at  last  the  patient  died  from  the  effects  of  the 
jaundice. 

Frerichs  has  reported  the  following  case.  After 
death  the  head  of  the  pancreas  was  found  enlarged 
and  completely  obstructing  the  ducts.  Old  capillary 
apoplexies  were  found  in  the  pons  Varolii.  The  man 
was  50  years  old  and  began  to  be  yellow  in  Decem- 
ber. No  suspicion  of  diabetes  seems  to  have  been 
aroused  until  about  March  15th,  when  it  was  dis- 
covered  that    the  patient  was   passing   sugar.        The 


*  Golowin,  Arch.  f.  path.  Anat.  1871,  Bd.  liii.  p.  428. 

f  Valmont,  Etude  sur  les  causes  des  variations  de  Vuree  dans  quelques  maladies 
dufoie,  These  de  Paris,  1879,  pp.  24,  et  seqq. 

\  Bright,  Med.  Chir.  Trans.  1833,  Vol.  xviii.  p.  3. 


278  Method  of  Testing  for  Bile  Pigment. 

quantity  was  never  more  than  5000  C.C.  in  the  24  hours 
and  the  specific  gravity  varied  from  loog  to  1018.  The 
amount  of  sugar  was  estimated  by  Soleil's  polarisation 
apparatus,  and  varied  from  -822  to  2'88  per  cent.  Three 
days  before  death  the  sugar  disappeared  from  the  urine, 
and  after  death  none  could  be  found  in  the  substance 
of  the  liver.*  Dr.  George  Harley  says  that  on  two 
occasions  he  found  a  little  sugar  in  the  urine  of  a  jaun- 
diced man,"]"  but  he  does  not  give  his  method  of  testing. 

It  is  a  matter  of  doubt  among  physiological  chemists 
whether  the  bile  pigments  be  not  natural  constituents 
of  the  urine.  It  is  acknowledged  generally  that  they 
may  be  found  in  the  urine  of  healthy  men  in  summer 
weather,  after  much  drink,  long-fasting,  &c.  In  the 
urine  of  many  animals,  such  as  dogs  and  cats,  there  is 
a  substance  almost  always  present  which  closely  imi- 
tates the  reaction  of  bile  pigment  with  nitric  acid. 

The  best  way  of  testing  for  bile  pigment  in  the  urine 
is  as  follows  :  ordinary  nitric  acid,  in  which  some  ni- 
trous acid  is  nearly  always  present,  is  poured  into  a  test 
tube  for  the  depth  of  an  inch.  On  to  the  surface  of  this 
the  urine  to  be  tested  is  gently  poured  by  means  of  a 
pipette,  down  the  side  of  the  tube,  so  that  the  two  fluids 
may  touch,  but  not  mix.  A  red  line  forms  at  the  place 
of  contact  in  every  urine.  If  the  urine  contain  bile  pig- 
ment, however,  a  zone  above  becomes  green,  then  blue, 
violet,  and  lastly  red,  the  uppermost  ring  being  green. 
This  colour  is  certainly  the  most  characteristic,  and 
without  it,  the  reaction  must  always  be  thought  dubi- 
ous. In  most  bilious  urines  only  the  green  colour  is 
seen.  The  varying  shades  of  colour  answer  to  the 
stages  of  oxydation  of  the  bile  pigment.  The  reaction 
is  known  by  the  name  of  Gmelin. 

Fleischl  says  that  it  is  now  common  to  practice  Gme- 

*  Frerichs,  op,  cit.  Bd.  i.  p.  153. 

f  George  Harley,  jaundice,  London,  1863,  pp.  78  and  79. 


Gmelin^s  Reaction.  279 

lin's  reaction  according  to  a  modification  of  Briicke's.* 
To  pure  nitric  acid,  obtained  by  boiling,  concentrated 
sulphuric  acid  is  cautiously  added.  The  sulphuric 
acid  from  its  great  specific  gravity  falls  to  the  bottom. 
It  hinders  the  too  rapid  developement  of  the  colours,  and 
the  reaction  gradually  spreads  upwards  from  the  line 
of  union  of  the  two  fluids,  instead  of  taking  place  simul- 
taneously throughout  the  liquid ;  all  the  different  colours 
may  be  seen  one  above  the  other.  Instead  of  pure  ni- 
tric acid,  a  solution  of  nitrate  of  sodium  may  be  used.f 

Carefully  practised,  it  is  by  far  the  best  test  for  bile 
pigment.  J  Other  methods  have  been  proposed,  as  that 
of  Marechal,  who  mixes  two  or  three  drops  of  tincture 
of  iodine  with  the  urine,  and  finds  an  emerald  green 
colour  given  to  the  fluid. §  This  test,  however,  is  lack- 
ing in  delicacy.  It  is  hard  to  perceive  the  green  colour 
when  the  amount  of  bile  pigment  is  small,  though  easy 
to  find  when  the  colour  of  the  urine  is  so  deep  as  not  to 
be  mistaken  for  anything  else  but  bilious  urine.  At  the 
beginning  and  end  of  an  attack  of  jaundice  the  iodine 
often  fails  when  the  nitric  acid  gives  a  distinct  green. 
Dr.  Walter  Smith,  however,  thinks  it  a  delicate  reac- 
tion. || 

Another  test  for  the  presence  of  bile  pigment  has 
been  lately  brought  forward,  violet  de  Paris,  or  methyl- 
anilin  violet.     It  appears,  however,  that  the  reaction 
seen   equally  well  with  urine   coloured  with  senna  or 
rhubarb,  or  by  the  carbolic  acid  treatment.     It  is  thus- 

*  Briicke,  Sitziingsberichte  d.  math.-naturw.  Classe  d.  k.  Akad.  d.  W,  Wien, 
1859,  Bd.  XXXV.  p.  14.     Briicke  himself  advises  dilute  nitric  acid. 

f  Fleischl,  Chem.  Centralblatt,  1S75,  p.  568  from  the  journal  of  Chemical 
Society. 

I  Rosenbach  {Centralblatt  f.  d.  med.  Wissenschaften,  1876,  p.  5)  proposes  a 
modification  of  Gmelin's  test.  Some  of  the  urine  is  filtered  through  filtering  paper 
and  then  a  drop  of  nitric,  acid  let  fall  on  the  paper  as  it  lies  in  the  funnel.  A  fine 
green  circle  is  developed. 

§  Marechal,  Journal  dc  Pharinacie  et  de  Chiniie,  1869,  4e  Serie,  t.  ix.  p.  i8g. 

II -Walter  G.  Smith,  Dublin  Journal  of  Medical  Science,  1876,  Vol.  Ixii.  p.  449. 


28o  Tests  for  Bile  Pigment. 

worthless  for  the  purpose  for  which  it  has  been  intro- 
duced.* 

Uhzmann  also  recommends  the  following  method : 
lo  C.C.  of  the  urine  are  mixed  with  3  or  4  C.C.  of  a  33 
per  cent,  of  caustic  potash  solution.  The  mixture  is 
then  acidified  with  pure  hydrochloric  acid  :  a  beautiful 
emerald  green  colour  is  seen  if  bile  pigment  be  present. "j* 

Stadeler  believes  that  the  chief  pigment  in  jaundiced 
urine  is  biliprasin  ;  because  the  urine  becomes  green 
with  acids  and  brown  with  alkalies,  and  solutions  of 
biliprasin  show  like  reactions. ;]:  On  the  other  hand, 
Schwanda,  from  numerous  observations,  asserts  that 
bilirubin  is  the  chief  pigment  in  jaundiced  urine,  and 
that  only  traces  of  biliprasin  can  be  found,  so  that  it 
is  the  bilirubin  which  is  the  chief  cause  of  colour,  not 
biliprasin. §  Stadeler's  test  is  not  nearly  so  delicate  as 
Gmelin's.  It  is  useful  sometimes  in  determining  if 
the  high  colour  of  the  urine  be  due  solely  to  drugs. 
Rhubarb  and  santonin  both  give  a  high  colour  to  the 
urine,  hardly  to  be  distinguished  by  the  eye  from  that 
of  jaundice.  Alkalies,  however,  deepen  to  a  red  the 
urine  passed  after  rhubarb  and  santonin,  but  give  a 
brown  colour  to  the  urine  of  jaundice. 

Schwanda  has  attempted  the  estimation  of  the  bili- 
rubin passed  in  the  urine,  and  if  his  results  may  be 
trusted,  the  amount  is  extremely  small,  even  in  cases 
where  the  urine  is  deeply  coloured.  The  greatest 
amount  found  was  '015  grm.  in  the  24  hours.  In  one 
case  it  was  as  little  as  '002  grm.||  Thus  the  largest 
amount  which  the  urine  contained  was  one  part  of  bile 

*  Gubler,  Gaz.  hchd.  1876,  p.  332.     See  also  p.  9  of  the  same  journal. 

f  Ultzmann,  Ccntralblatt  f.  d.  mcd.  Wiss.  1877,  p.  831. 

X  Stadeler,  Aiinalcn  d.  Chcm.  u.  Pharm.  1864,  Bd.  cxxxii.  p.  341.  According  to 
Stadeler,  the  formula  for  biliprasin  is  C32H22N2012  ;  for  bilirubin,  C32Hi8N20e. 
Maly  suggests  that  biliprasin  and  biliverdin  are  identical.  {Journ.f.  pvak.  Chcm, 
1868,  Bd.  civ.  p.  32.) 

§  Schwanda,  Wiener  mcd.  Wochcnschrift,  1865,  p,  692. 

II  Schwanda,  op.  cit.  p.  989. 


Tests  for  Bile  Pigment.  281 

pigment  in  100,000  parts  of  urine.  Even  if  these  re- 
sults be  only  approximately  true,  the  amount  of  pigment 
passed  must  be  very  small  in  comparison  with  the  pig- 
ment excreted  in  health  by  the  liver. 

In  some  cases  of  jaundice,  even  wh&n  the  urine  is 
high  coloured  and  clearly  contains  abundance  of  some 
kind  of  pigment,  no  reaction,  or  no  distinctive  reaction, 
with  nitric  acid  can  be  seen.  Prussak  believes  that 
this  absence  of  reaction  is  due  to  the  presence  of  fever, 
and  that  the  bile  pigments  are  burnt  off  or  oxydised  in 
the  blood  so  that  they  can  no  longer  be  detected  in  the 
urine.*  Huppert,  again,  says  that  in  many  cases  of 
jaundice,  no  pigment  but  biliprasin  can  be  found  during 
the  whole  course  of  the  disease,  and  it  is  to  the  absence 
of  any  other  pigment  but  biliprasin  that  the  trouble  in 
applying  the  nitric  acid  test  is  due.f  These  two  state- 
ments are  not  contrary,  as  biliprasin  is  but  a  more 
highly  oxydised  body  than  bilirubin;  yet  Stadeler  affirms 
that  bihprasin  gives  all  the  reactions  of  bile  pigments 
with  nitric  acid,  saving  only  that  the  blue  colour  is  in- 
distinct.:|:  Frerichs  likewise  attributes  the  failure  of  the 
nitric  acid  reaction  to  an  oxydation  either  in  or  out  of 
the  body.§  Nitric  acid  only  gives  in  this  case  a  red 
colour. 

*  Prussak,  Centralblatt  f.  d.  mcd.  Wiss.  1867,  p.  97. 

f  Huppert,  Arch.  d.  Heilkunde,  1867,  Jahrg.  viii.  pp.  351  and  476.  This  writer 
finds  the  best  plan  of  recognising  even  traces  of  bile  pigment  in  the  urine  is  to 
precipitate  with  milk  of  lime,  let  the  mixture  stand,  and  filter.  Some  of  the 
precipitate,  the  size  of  half  a  hazel  nut,  is  put  into  a  test  tube,  and  the  test  tube 
half  filled  with  absolute  alcohol,  and  dilute  sulphuric  acid  added  till  the  fluid  have 
a  distinct  acid  reaction.  A  precipitate  is  slowly  thrown  down  of  a  greenish  colour; 
and  if  the  fluid  be  gently  warmed,  the  alcohol  itself  becomes  of  a  greenish  colour. 
Hilger  recommends  that  50  to  100  C.C.  of  the  urine  be  gently  warmed,  and  hydrate 
of  baryta  added  until  an  alkaline  reaction  appear.  The  precipitate  is  collected 
and  washed  :  if  sprinkled  with  nitric  acid  the  well-known  colours  are  seen.  Or 
the  precipitate  may  be  heated  with  solution  of  carbonate  of  soda,  when  the  pig- 
ments pass  into  the  solution,  and  it  acquires  a  green  or  brownish-green  colour. 
(Hilger,  jfoiirnal  of  Chemical  Society,  1876,  Vol.  i.  p.  445.) 

X  Stadeler,  lac.  cit. 

§  Frerichs,  op.  cit,  Bd,  i.  p.  106. 


282  Presence  of  Bile  A  cids 

Lewin  states  that,  when  jaundiced  urine  gives  no 
reaction  with,  nitric  acid,  the  reaction  may  sometimes 
be  seen  on  cooUng  the  urine  with  ice',  thus  causing  a 
precipitation  of  the  urates,  collecting  the  urates  on  a 
filter,  dissolving  them  in  warm  water,  and  testing  this 
solution  with  nitric  acid.  A  beautiful  Gmelin's  reaction 
may  thus  be  seen.*  These  observations  closely  agree 
with  those  of  Ernst  Bischoff,  who  found  a  large  amount 
of  pigment  thrown  down  with  the  uric  acid  after  acidu- 
lation. 

Although  the  presence  of  one  element  of  the  bile, 
the  pigment,  is  plain  almost  to  the  unaided  senses  with- 
out chemical  help,  yet  it  is  quite  otherwise  with  another 
important  element  of  the  bile,  the  conjugate  acids. 
Before  the  days  of  Pettenkoferf  and  StreckerJ  it  was 
well  nigh  hopeless  to  search  for  these  crystalline  elements 
of  the  bile  in  the  urine.  Nevertheless  some  observers 
thought  they  had  detected  them  both  in  the  blood  and 
urine  of  jaundice.  After  Pettenkofer,  none  succeeded§ 
in  finding  the  bile  acids  in  the  urine,  notwithstanding 
many  attempts  by  observers  in  every  way  worthy  of 
credit.  It  was  therefore  assumed  that  the  bile  acids 
were  absent  from  the  urine  in  jaundice,  and  it  be- 
came a  matter  of  importance  to  explain  their  absence. 
Frerichs  and  Stadeler  found  that  after  the  injection  of 
colourless  bile  into  the  veins  of  animals,  the  urine  was 
tinged  of  a  high  colour,  and  gave  a  well-marked  re- 
action with  Gmelin's  test,  showing  the  presence  of  bile 
pigmentll  and  yet  no  bile  acids  could  be  found  in  this 

*  Lewin,  Centralblatt  f.  d.  nied.  Wiss.  1875,  p.  81. 

f  Pettenkofer,  Annalen  d.  Chemic  u.  Phartn.  1S44,  Bd.  lii.  p.  90. 

X  Adolph  Strecker,  ibid.  1848,  Bd.  Ixv.  p.  i. 

§  C.  G.  Lehmann,  however,  says  {Lelirb.  d.  phys.  Chemic,  Leipzig,  1853,  ate 
Aufl.  Bd.  i.  p.  122.)  that  he  has  found  substances,  which  give  Pettenkofer's  re- 
action, in  the  blood  and  urine  of  persons  whose  livers  did  not  seem  immediately 
concerned  in  the  disease. 

II  Frerichs,  op.  cit.  Bd.  i.  p.  404.  I  have  elsewhere  (p.  235.)  remarked  npon  the 
incorrectness  of  this  observation. 


in  the  Urine  of  Jaundice.  283 

urine.  The  same  observers  afterwards  found  that  when 
sulphuric  acid  was  allowed  to  act  upon  the  bile  acids, 
a  coloured  substance  was  seen,  which  gave  with  nitric 
acid  the  same  play  of  colours  as  bile  pigment.*  Here 
there  seemed  a  clear  way  out  of  all  difficulties.  The 
bile  acids  do  not  appear  in  the  urine,  because  they  are 
oxydised  in  the  circulation  into  bile  pigment. 

But  in  1858,  two  years  after  the  publication  of  this 
last  discovery,  Hoppe  detected  in  jaundiced  urine  a 
notable  quantity  of  choloidic  acid,  an  acid  derived 
from  the  bile  acids,  but  containing  no  nitrogen,  and 
yet  giving  Pettenkofer's  reaction. "j"  Later  on  he  de- 
monstrated the  presence  of  nitrogenous  derivatives  from 
the  bile  acids, J  and  last  of  all,  the  presence  of  glyco- 
cholic  and  taurocholic  acids  themselves,  together  with 
cholalic  acid,  in  the  urine  of  jaundice.  § 

This  discovery  of  the  bile  acids  or  their  derivatives 
in  the  urine  was  soon  after  confirmed  by  Kuhne,||  and 
although  at  first  doubted  by  some,^  yet  these  acids 
have  been  so  repeatedly  found  by  those  who  have  used 
Hoppe's  improved  method  of  searching  for  them,  that 
their  presence  in  the  urine  of  jaundice  is  now  generally 
admitted. 

It  may  be  doubted  if  the  total  amount  of  bile  acids  in 
the  urine  have  ever  been  properly  estimated.  It  is  at 
all  events  so  small  that  Pettenkofer's  test  applied  di- 
rectly to  the  urine  gives  no  certain  result.  Hoppe  in 
a  case  of  acute  yellow  atrophy  found  about  "03  per  cent. 
of  cholonic  acid  ;**  and  Ernst  Bischoff  gives  as  the 
result  of  three   estimations,  '02,   "04,  and  '05  per  cent. 


*  Frerichs  and  Stadeler,  Arch.f.  Anat.  Phys.  S'C.  1856,  p.  55. 

f  Hoppe,  Arch.  f.  path.  Anat.  1858,  Bd.  xiii.  p.  loi. 

J  Idem,  ibid.  1862,  Bd.  xxiv.  p.  i. 

§  Hoppe-Seyler,  Ccntralblattf.  d.  med.  Wiss.  1863,  p.  337. 

II  Kiihne,  Arch.  f.  path.  Anat.  1858,  Bd.  xiv.  p.  315. 

IT  Neukomm,  Arch.f.  Anat.  Phys.  &'c.  i860,  p.  368. 

**  Hoppe,  Arch.  f.  path.  Anat.  1862,  Bd.  xxiv.  p.  8. 


284  Method  of  looking  for  Bile  A  cids 

This  latter  observer  looks  upon  "3  grm  as  the  maximum 
of  bile  acids  excreted  in  jaundice  by  the  urine  during 
the  24  hours,*  a  result  which  agrees  generally  with 
that  of  Hoppe-Seyler. 

If  Pettenkofer's  test  be  applied  directly  to  many  urines, 
a  reaction  follows  which  may  readily  be  confounded  with 
that  seen  in  a  pure  solution  of  bile  acids.  Sulphuric 
acid  by  itself,  without  the  presence  of  sugar,  will  often 
cause  a  fine  red  or  purple  colour,  by  inexperienced  eyes 
easily  to  be  mistaken  for  Pettenkofer's  reaction.  This 
is  most  often  the  case  in  a  high  coloured  or  albuminous 
urine,  and  is  not  uncommon  in  perfectly  natural  urine. 
Nothing  therefore  but  disappointment  and  utterly  un- 
trustworthy results  can  be  looked  for  from  the  direct 
application  of  Pettenkofer's  test  to  jaundiced  urine. 
It  is  a  method  which  should  never  be  adopted.  The 
bile  acids  must  be  separated  out  from  the  jaundiced 
urine  before  their  presence  can  be-  definitely  asserted. 
Neukomm  has  found  that  urine  to  which  i  per  cent,  of 
bile  acid  had  been  added  gave  with  sulphuric  acid  and 
sugar  a  reaction  not  to  be  distinguished  from  that  given 
with  sulphuric  acid  alone  by  the  same  urine  to  which  no 
bile  acid  has  been  added.  The  Pettenkofer's  reaction 
only  became  unequivocal  when  the  urine  contained  '5 
per  cent,  an  amount  greatly  exceeding  that  ever  seen  in 
the  urine  of  jaundice. f 

To  detect  the  bile  acids  in  jaundiced  urine  a  long 
preparation  is  needed.  In  Hoppe's  first  experiments, 
the  urine  was  boiled  with  milk  of  lime,  then  filtered, 
and  again  boiled  with  hydrochloric  acid.  This  un- 
doubtedly causes  a  large  destruction  of  the  bile  acids, 
and  the  method  which  is  now  recommended  is  as  fol- 
lows :  Precipitate  the  bile  acids  with  acetate  of  lead 
from  the  urine,   made   faintly  ammoniacal :    wash  the 

*  Ernst  Bischoff,  Zcitschriftf.  rat.  Med.  1864,  Bd.  xxi.  p.  140. 

f  Neukomm,  Annalcn  d.  Chemie  nnd  Pharmacic,  i86o,  Bd.  cxvi.  p.  34. 


in  the  Urine  of  Jaundice.  285 

precipitate  with  a  little  water,  boil  it  with  alcohol,  and 
filter  hot.  The  lead  salts  of  the  bile  acids  are  soluble 
in  hot  alcohol ;  a  few  drops  of  soda  solution  should 
next  be  added,  and  the  whole  evaporated  to  dryness. 
This  should  now  be  boiled  with  absolute  alcohol,  filtered 
and  evaporated  to  a  small  volume,  and  then  poured 
into  a  great  excess  of  aether.  In  this  way  the  bile  acids 
may  often  be  crystallised  out.* 

This  process  is  troublesome,  and  ill  fitted  for  the 
wants  of  the  practitioner.  Modifications  of  it  have  been 
proposed.  A  rapid  way  of  testing  has  been  set  forth  by 
Strassburg.  A  piece  of  filtering  paper  is  dipped  into  the 
urine  to  be  tested,  to  which  a  little  cane  sugar  has  been 
added.  The  paper  is  then  dried,  and  on  the  centre  is 
let  fall  a  drop  of  concentrated  sulphuric  acid.  Around 
the  drop  of  acid  a  beautiful  violet  colour  forms. "j*  In 
my  own  hands,  however,  this  test  has  proved  very 
unsatisfactory.  I  have  noticed  a  purplish  colour,  iden- 
tical with  that  seen  with  jaundiced  urine,  arise  with 
natural  urine,  or  with  urine  from  patients  not  known  to 
;have  anything  amiss  with  their  livers. 

Hilger  recommends  a  modification  of  Hoppe-Seyler's 
method.  The  urine  is  mixed  directly  with  basic  acetate 
of  lead  and  ammonia ;  and  the  precipitate  is  then  dried 
at  a  low  heat  and  again  and  again  warmed  with  abso- 
lute alcohol.  The  alcoholic  extract  is  decomposed  with 
carbonate  of  soda,  evaporated  to  dryness,  and  again 
taken  up  by  warm  alcohol.  The  bile  acid  salts  are 
then  thrown  by  aether,  in  the  usual  way. J 

By  some   observers  the  bile   acids  are    now   looked 

*  Hoppe-Seyler,  Handb.  d.phys.-  u.  path.-chem.  Analyse,  Berlin,  1865,  2te  Aufl. 
p.  274. 

f  Strassburg,  Arch.  f.  d.  ges.  Phys.  1871,  Bd.  iv.  p.  461.  See  also  p.  5  of  this 
work. 

I  Hilger,  yournal  of  the  Chemical  Society,  1876,  Vol.  i.  p.  445.  Another  method 
for  recognising  bile  is  given  by  Casali  in  La  Scienza  applicata,  1876,  I.  fasc.  6. 
quoted  in  Centralblatt  f.  d.  med.  Wiss.  1878,  p.  583. 


286  Bile  Acids  found  in  Natural  Urine. 

upon  as  natural  constituents  of  the  urine.  Naunyn 
collected  large  quantities  of  natural  urine  and  was  able 
to  detect  an  appreciable  amount  of  bile  acids  by  the 
process  of  precipitation  with  lead.*  Fudakowskif  HoneJ 
and  Vogel  have§  repeated  and  confirmed  these  observa- 
tions, but  their  value  has  been  doubted  by  Wolff.  || 

The  presence  of  the  bile  acids  in  natural  urine,  if 
granted,  is  probably  due  to  an  absorption  of  the  bile 
acids  from  the  intestine,  a  very  small  quantity  passing 
through  the  liver  into  the  general  circulation. 

It  has,  however,  been  asserted  of  late  that  in  long 
continued  jaundice  the  liver  loses  the  power  of  secreting 
the  bile  acids,  and  thus  none  appears  in  the  urine. 
Golowin  found  none  either  in  men  or  animals. ^J  Hup- 
pert  found  the  amount  much  decreased  towards  the  end 
of  a  case  of  acute  yellow  atrophy:**  and  Dr.  Pye-Smith 
could  find  no  bile  acids  in  14000.  C.  C.  of  the  urine  of 
a  patient  jaundiced  a  long  time,  probably  from  gall- 
stones.tf 

Neither  dyslysin,  norglycocoll  or  taurin  has  ever  been 

found  free  in  the  urine. §§  The  first  is  a  product  of  the 
decomposition  of  the  bile  acids ;  the  two  last  are  impor- 
tant constituents  of  glycocholic  and  taurocholic  acid. 

*  Naunyn,  Arch  f.  Anat.  Phys.  dfc.  1868  p.  430. 

f  Fudakowski,  Ccntralhlatt  f.  d.  med.  Wiss.  1S69,  p.  I2g. 

J  Hone,  ibid,  1874,  p.  872. 

§  Vogel,  Schmidt's  yahrhb.  1872,  Bd.  clvi.  p.  36.  Dragendorff  was  able  to  get 
•7  or  "8  grm.  of  bile  acid  from  100  litres  of  urine,  {Zcitschrift  f.  anal.  Clicm.  1872, 
Bd.  xi.  p.  467.) 

II  F.  A.  Wolff,  Zjir  Pathologic  dcs  Ikterus,  Diss.  Inaug.  Konigsberg,  1869.  Abs- 
tract in  Henle  and  Meissner's  Bericht  f.  i86g,  p.  196. 

II  Golowin,  Arch.f.  path.  Anat.  1871,  Bd.  liii,  p.  433. 

**  H.  Huppert,  Arch.  d.  Heilk.  1864,  Bd.  v.  p.  255. 

ff  Pye-Smith,  Trans,  of  Path.  Soc.  of  Lond.  1873,  Vol.  xxiv.  p.  251.  He  does 
not,  however,  give  the  method  followed. 

§§  Frerichs,  op.  cit,  Bd.  i.  p.  102,  note.  Ernst  Bischoff,  Zcitschrift  f.  rat.  Med. 
1864,  3te  Reihe,  Bd.  xxi.  p.  146.  Kiihne,  Arch.f.  path.  Anat.  1858,  Bd.  xiv.  p.  322. 
I  attribute  no  value  to  the  finding  of  taurin  in  the  urine  by  Raczieiewsky,  (Leyden, 
Bcitrdgc  zur  Path,  dcs  Icterus,  Berlin,  1866,  p.  33),  as  the  microscope  only  was  used 
and  no  chemical  test. 


A  mount  of  Urea  Excreted.  287 

Krusenstern  sought  in  the  urine  for  cholestearin  in 
four  cases  of  jaundice  as  well  as  in  other  disorders  ;  but 
found  none.* 

The  amount  of  urea  excreted  in  jaundice  has  of  late 
years  been  much  studied,  especially  in  Paris.  For  it 
would  seem  likely  if  Meissner's  theory  of  the  formation 
of  urea  in  the  liver  be  true,  that  the  amount  of  urea  in 
jaundice  would  be  decreased ;  and  on  these  grounds  : 
if  albuminous  substances  be  split  up  in  the  liver 
into  glycogen,  bile  acids  and  urea,  then,  if  the  for- 
mation of  glycogen  cease  in  jaundice,  the  formation 
of  urea  should  cease  likewise.  I  have  shown  that 
within  a  few  hours  after  the  ligature  of  the  bile 
ducts  glycogen  ceases  to  be  found  in  the  liverf  and 
this  statement  has  been  confirmed  by  von  Wittich.J 
If  then  in  jaundice  no  glycogen  is  formed  by  the  liver, 
it  would  seem  likely  that  the  urea  and  bile  acids  would 
likewise  cease  to  be  made.  Now  Golowin  certainly 
seems  to  think  that  in  long-continued  jaundice,  the  bile 
acids  no  longer  appear  in  the  urine  ;§  and  the  fluid 
found  in  the  dilated  gall  ducts  after  death  often 
gives  no  reaction  with  Pettenkofer's  test.  But  these 
are  all  cases  in  which  the  jaundice  has  been  long 
continued,  and  it  is  denied  by  none  that  early  in 
jaundice,  bile  acids  may  readily  be  found  in  the  urine 
and  in  the  biliary  passages.  So  that  notwithstanding 
Golowin's  statement  it  would  seem  likely  that  in  jaun- 
dice, at  all  events  early  in  the  disease,  the  bile  acids 
continue  to  be  formed.  As  to  the  urea,  much  doubt 
formerly  existed  whether  the  amount  were  usually  low 
or  natural.  Becquerel  analysed  the  urine  of  three 
jaundiced   patients.      In  the   first,    a   man,    he   found 


*  Krusenstern,  Arch./,  path.  Anat.  1875,  Bd.  Ixv.  p.  415. 

f  Wickham  Legg,  St.  Bartholomew's  Hospital  Reports,  1873,  Vol.  ix.  p.  161. 

X  Von  Wittich,  Centralblatt  f.  d.  med.  Wiss.  1875,  p.  291. 

§  Golowin,  Arch.  f.  path.  Anat.  1871,  Bd.  liii.  p.  433: 


288  Amount  of  Urea  Excreted. 

17-923  grm.  was  excreted  in  the  24.  hours ;  in  the 
second,  a  man  jaundiced  after  a  violent  dispute,  he 
found  only  4*037  grm.  and  in  a  third,  a  pregnant 
woman,  markedly  jaundiced,  7*933  grm.* 

A.  Voeel  found  in  a  case  of  cancer  of  the  liver 
with  jaundice  that  the  urea  varied  from  6*75  to  9*5 
grm,  a  very  low  amount. f  KoUiker  and  Miiller 
found  in  a  woman  aged  25  with  simple  jaundice 
that  the  mean  of  urea  during  the  jaundice  was  20 
grm.,  during  convalesence  19  grm.,  and  when  in 
health  26  grm. J  Leyden,  on  the  other  hand,  has 
recorded  a  case  in  which  the  urea  once  rose  to  50 
grm.  in  the  24  hours  ;  three  times  it  is  noted  between 
30  and  46  grm.  and  it  never  fell  below  23  grni.§ 
There  seems  to  have  been  in  this  case  some  rela- 
tion between  the  amount  of  water  excreted  and  the 
urea  ;  the  highest  readings  of  urea  corresponding  to 
the  highest  readings  of  water  and  vice  versa.  Bouchardat 
has  recorded  an  extraordinary  case  in  which  the 
readings  of  the  urea  were  enormously  high.  A  man 
with  simple  jaundice,  following  a  sudden  great  joy, 
passed  3750.  C.  C.  of  urine  in  the  twenty-four  hours  : 
the  specific  gravity  was  1031.  The  amount  of  solid 
matter  passed  was  220*87  grm  :  the  urea  I33'6  grm. 
The  jaundice  next  day  was  less,  and  the  urea  only 
89*18  grm.  On  the  third  day  the  jaundice  was  still  less 
and  the  urea  only  46*94  grm.||  The  same  observer  has 
recorded  another  instance  of  uncomplicated  jaundice  in 
which  the  urea  ruled  high,  57*2  grm.  in  the  24  hours. ^ 

*  Becquerel,  Scmciotique  des  Urines,  Paris,  1841,  pp.  413,  and  393.  There  is  an 
old  analysis  of  Braconnot  in  which  he  says  he  found  more  urea  and  less  phosphate 
of  lime  than  usual,    (jfournal  de  chimic  mid.  1827,  t.  iii.  p.  480.) 

t  A.  Vogel,  Zeitschriftf.  rat.  Med.  1854,  Bd.  iv.  (neue  Folge)  p.  391. 

+  Kolliker  and  Miiller,  Verhandlungen  d.  phys.  med,  Gesellscha/t  in  Wiirzburg, 
1856,  Bd.  vi.  p.  497. 

§  Leyden,  Bcitrdge  ziir  Path.  d.  Icterus,  Berlin,  1866,  p.  205. 

II  Bouchardat,  J^nnuaire  de  Therapcutiqnc,  1846,  p.  328. 

%  Idem,  ibid.  i86g,  p.  237. 


Amount  of  Urea  Excreted.  289 

Genevoix  has  published  7  cases  of  simple  jaundice  in 
which  during  the  height  of  the  jaundice  the  urea  was 
markedly  increased,  falling  to  the  natural  standard  as 
the  jaundice  disappeared.  In  three  of  these  cases  the 
urea  was  over  60  grm.  in  the  24  hours  ;  in  two,  55  grm. 
and  in  the  remaining  two,  45  grm.  When  convales- 
cence was  established,  the  amount  fell  to  23  or  24  grm. 
There  was  no  rise  of  temperature.*  Reuflet  records 
another  case  of  simple  jaundice  in  which  the  attack 
followed  violent  anger,  and  on  the  third  day  of  the  dis- 
ease the  amount  of  urea  was  41  grammes  in  1800  C.C. 
of  urine.  The  amount  of  urea  ruled  high  until  the 
jaundice  began  to  disappear,  when  it  sank  to  27  and 
26  grammes  in  the  24  hours.  Reuflet  founds  a  the- 
ory on  this  observation,  and  those  of  Bouchardat  and 
Brouardel.  He  thinks  that  if  there  be  no  injury  to 
the  liver  cells,  but  an  increase  of  the  circulation  in  the 
liver,  a  state  which  he  assumes  in  simple  jaundice,  then 
the  amount  of  urea  is  much  increased  ;  but  if  the  liver 
cells  be  injured,  or  the  circulation  become  slow,  then 
the  urea  is  diminished. t 

Brouardel  has  analysed  the  urine  of  three  cases  of 
simple  jaundice,  and  found  no  increase  or  decrease  of 
urea.  His  figures  vary  from  26  grm.  to  32"8  grm. 
daily. J  Julius  Jacobs  has  estimated  the  urea  in  three 
cases :  in  one,  complete  obstruction  of  the  ducts  from 
a  mass  of  cancer  was  present,  and  the  amount  of  urea 
was  on  an  average  of  7  days,  56*525  grm.  in  the  24 
hours.  In  two  other  cases  it  was  28*249  grm.  and 
27*527  grm.  on  an   average. §      Dr.  A.  W.  Foot  found 

*  Genevoix,  Essai  stir  les  variations  de  Vuree  et  Vacide  urique  dans  les  maladies 
dnfoie,  Paris,  1876,  p.  63. 

f  Reuflet,  Contribution  a  V etude  du  role  du  foie  dans  la  production  de  Vuree, 
These  de  Paris,  1879.  pp.  33  and  54. 

X  Brouardel,  Archives  de  Physiologie,  1876,  p.  416, 

§  Julius  Jacobs,  Arch.  f.  path.  Anat.  1877,  Bd.  Ixix.  p.  487. 

U 


2 go  Amount  of  Urea  excreted 

no  decrease  of  the  amount  in  one  of  his  cases.*  Nor 
did  Dr.  George  Harley  in  a  case  of  jaundice  lasting 
1 8  months  find  any  decrease  until  a  fortnight  before 
the  death  of  the  patient. t 

In  three  cases  of  supposed  cirrhosis  complicated 
with  jaundice,  Valmont  found  the  average  of  the  urea 
to  be  in  one,  i8  grammes,  in  the  second,  15  grammes, 
in  the  third,  7  grammes.  In  a  fourth  case  of  jaundice 
supposed  to  be  due  to  cancer  of  the  liver,  the  mean  was 
13  grammes. J  Vulpian  found  in  a  case  of  cirrhosis 
with  jaundice,  that  the  mean  was  26'84g  grm.§ 

In  three  cases  of  jaundice  with  clay-coloured  stools, 
J.  C.  Lehmann  found  the  amount  of  urea  decreased 
during  the  obstruction  to  the  gall  ducts,  while  it  be- 
came greater  as  soon  as  the  obstruction  was  removed. 
In  the  third  case,  the  amount  of  urea  was  increased.  || 
Lehmann  explains  the  diminution  by  supposing  an  im- 
perfect digestion  of  the  albuminous  matters,  probably 
because  the  parapeptones  are  not  thrown  down.  What, 
however,  would  be  the  explanation  of  the  cases  in 
which  the  urea  is  increased  in  amount  ? 

I  have  made  observations  upon  the  urea  in  ten  cases 
of  jaundice.  The  two  cases  in  which  the  largest 
amount  of  urea  was  passed  were  likewise  those  in  which 
the  largest  amount  of  water  was  passed,  and  in  which 
the  jaundice  had  been  longest  and  most  intense.  The 
mean  of  the  urea  in  these  two   cases  was   28"387  and 


*  A,  W.  Foot,  Dublin  Journal  of  Medical  Science,  1876,  Vol.  Ixi.  p.  478.  The 
amount  excreted  was  439'o87  grains. 

f  George  Harley,  Jaundice,  its  pathology  and  treatment,  London,  1863,  p.  74 
et  seqq. 

I  Valmont,  Etude  sur  Ics  causes  des  variations  de  Vurce  dans  quelques  maladies 
dufoie.  These  de  Paris,  1879.  This  thesis  has  been  put  together  with  much  dili- 
gence, and  contains  a  long  series  of  analyses  of  the  urine,  chiefly  in  cases  of  cir- 
rhosis.    The  estimations  of  the  urea  were  made  by  the  hypobromite  process. 

§  Vulpian,  Clinique  med.  Paris,  1879.  p.  272. 

II  J.  C.  Lehmann,  Ugeskr.for  Lager,  1868,  3  R.  vi.  No.  24-26.  Abstract  in 
Virchow's  Jahresb.f.  1868,  Bd.  ii.  p.  143. 


in  the  Urine  of  Jaimdice.  291 

29*574  girn.  The  lowest  amount  of  urea  was  met  with 
in  a  case  of  somewhat  uncertain  diagnosis,  in  which 
the  jaundice  had  lasted  about  two  months  and  the 
stools  were  of  a  light  brown  ;  the  mean  of  five  consecu- 
tive observations  was  I5"975  grm.  In  two  other  cases 
of  jaundice  from  cancer  of  the  pancreas  and  liver,  the 
mean  amount  of  six  observations  was  18  grm.  In  the 
remaining  five  cases,  the  means  varied  from  19*8  to 
27*28  grm.* 

Upon  a  review  of  these  cases  it  seemed  to  me  that 
the  amount  of  urea  was  the  greatest  in  those  patients 
whose  general  health  was  the  best,  or  who  were  allowed 
the  most  generous  diet.  I  do  not  think  there  is  any- 
proof  that  obstruction  of  the  gall  ducts  causes  a  les- 
sened excretion  of  urea  ;  although  the  earlier  recorded 
cases  may  at  first  seem  to  encourage  such  a  belief. 
Some  of  the  estimations  of  the  urea  lately  undertaken 
by  the  French  observers,  apparently  at  the  suggestion 
of  Charcot,  seem  to  destroy  such  a  notion.  It  is,  how- 
ever, a  hard  matter  on  any  theory  to  explain  the  great 
increase  of  urea  which  Bouchardat  noted  in  his  cases, 
and  it  only  remains  to  remark  that  according  to  present 
observations  the  urea  in  jaundice  may  be  low,  natural, 
or  greatly  in  excess  ;  and  that  the  laws  which  govern 
the  amount  of  the  urea  in  the  urine  of  jaundice  are  yet 
quite  unknown. 

Baumstark  found  in  the  urine  of  jaundice  a  homo- 
logue  of  ordinary  urea,  which  he  looks  upon  as  the 
diamide  of  sarcolactic  acid,  or  the  urea  of  sarcolactic 
acid.  This  body  is  also  present  in  normal  urine,  but 
in  small  quantity.f 

There  are  not  many  observations  on  the  amount  of 
uric  acid   daily  excreted  in  jaundice.     Becquerel  found, 

*  Wickham  Legg,  Med.  Chir.  Trans.  1876,  Vol.  lix.  p.  149. 

f  Baumstark,   Berichte   d.   deiitschen  chemischen  Gesellschaft  zn  Berlin,   1873, 
Bd.  vi.  p.  1378. 

U  2 


292  Amount  of  Uric  Acid 

in  one  of  three  cases,  the  uric  acid  in  excess,  as  much 
as  1*153  g^^-  ii^  quantity,*  but  in  the  remaining  two  it 
was  natural.  Kiihne  seems  to  think  that  it  is  always 
much  increased, t  and  on  the  other  hand,  Ernst  Bischoff, 
whose  observations  lay  claim  to  far  greater  accuracy  than 
those  of  Kiihne,  found  the  uric  acid  not  increased.  J  He 
explains  Kiihne's  statement  by  saying,  that  when  jaun- 
diced urine  is  acidulated  with  hydrochloric  acid,  an 
amazing  quantity  of  crystals  is  thrown  down.  If  these 
crystals  be  collected  on  a  filter,  they  dissolve  when  well 
washed  with  water,  and  the  water  gives  an  intense 
reaction  with  nitric  acid  ;  so  that  it  is  highly  probable 
that  the  crystals  are  mostly  made  up  of  bile  pigment. 
Dr.  A.  W.  Foot  has,  however,  in  one  case  found  an  in- 
crease of  the  uric  acid,  the  amount  being  27*13  grains. § 
Dr.  George  Harley  found  *5ii  and  "266  grm.,  and  lastly 
none,  in  three  analyses  made  one  after  another  in  a  case 
of  permanent  obstruction. ||  In  these  two  last  cases  the 
uric  acid  seemed  to  diminish  or  increase  pari  passu  with 
the  urea.  The  like  was  noticed  by  Genevoix  who  found 
that  the  uric  acid  was  increased  in  7  cases  of  simple 
jaundice  with  the  urea,  and  that  as  the  jaundice 
diminished  the  urea  and  uric  acid  decreased  likewise. 5[ 
Julius  Jacobs  did  not  find  the  uric  acid  diminish  or  in- 
crease with  the  urea  :  his  lowest  reading  is  '997  grm. 
while  the  urea  is  56*525  grm.,  while  in  the  two  other 
cases  the  uric  acid  is  1-0038  and  1*466  to  28*249  and 
27*527  of  urea.**  In  Valmont's  four  cases,  three  of 
cirrhosis  and  one  of  cancer,   the  uric  acid  was,  if  any- 

*  Becquerel,  Senieiotique  des  Urines,  Paris,  1841,  pp.  393  and  413. 

f  Kuhne,  Arch.  f.  path.  Anat.  1858,  Bd.  xiv.  p.  320. 

X  Ernst  Bischoff,  Zcitschr.f.  rat.  Med.  1864,  Bd.  xxi.  p.  151. 

§  A.  W.  Foot,  loc.  cit. 

II  George  Harley,  loc.  cit.  and :  "  In  non-malignant  hepatic  disease,  especially 
towards  its  latter  stages,  the  uric  acid  is  found  to  be  remarkably  diminished." 
{Urine  and  its  derangements,  1872,  London,  p.  71.) 

H  Genevoix,  loc.  cit. 

•*  Julius  Jacobs,  Arch./,  path.  Anat.  1877,  Bd.  Ixix.  p.  487. 


mid  of  Chlorides  excreted.  293 

thing,  below  the  bounds  of  health;  but  in  many  analyses 
it  rose  and  fell  with  the  urea.* 

Kiihne  stated,  in  the  midst  of  his  essay  on  jaundice, 
that  no  hippuric  acid  could  be  found  in  the  urine  of 
jaundiced  men  ;  and  that  after  benzoic  acid,  or  its  soda 
salts,  had  been  given  to  jaundiced  patients,  no  hippuric 
acid  appeared  in  the  urine,  but  only  unchanged  benzoic 
acid.f  It  is  well  known  that  if  benzoic  acid  be  given 
to  men  in  health,  an  equivalent  quantity  of  hippuric 
acid  appears  in  the  urine.  Several  observers  have  re- 
peated Kiihne's  experiments,  but  all  with  a  negative 
result.  J  The  source  of  error  in  Kiihne's  work  seems 
to  be  that  the  urine  was  not  examined  while  quite  fresh, 
and  that  the  hippuric  acid  was  changed  again  into 
benzoic.  The  hippuric  acid  may  in  all  cases  be  found 
in  jaundiced  urine,  if  looked  for  soon  after  the  urine 
have  been  voided,  and  by  the  method  recommended 
by  Schultzen. 

Less  attention  has  been  paid  to  the  chlorides  than  to 
the  uric  acid.  A.  Vogel  found  them  in  his  case  greatly 
decreased.  They  were  only  '16  to  '3  grm:  in  the 
twenty-four  hours. §  In  g  cases  of  jaundice  in  which 
I  estimated  the  chlorides,  I  found  a  tolerably  close  re- 
lation to  the  urea,  the  chlorides  being  equal  to  about 
one  half  of  the  urea  in  6  out  of  the  g.  In  2  of  these  3 
cases  the  chlorides  were  decreased ;  they  were  both 
cases  of  cancer  of  the  pancreas  ;  the  chlorides  were 
about  6  grm.  to   18  and  22   grm.  of  urea.     In  the  re- 

*  Valmont,  Etude  stir  les  causes  des  variations  de  Vuree,  etc.  These  de  Paris, 
1879. 

f  Kiihne,  Arch.  f.  path.  Anat.  1858,  Bd.  xiv.  p,  319. 

X  Folwarczny,  Zeitschr.  d.  k.k.  Gesellschaft  d.  Aerzte  zu  Wien,  1859,  p.  225. 

Schultzen,  Arch.  f.  Anat.  Phys.  &'c.  1863,  p.  204. 

Neukomm,  Frerichs'  Klinik  d.  Leberkrankheiten,  Bd.  ii.  p.  537. 

Huppert,  Arch.  d.  Heilkunde,  1865,  p.  93. 

Horace  Chase,  Arch.f.  Anat.  Phys.  &'c.  1865,  p.  392.  In  two  of  Chase's  cases, 
however,  (dogs  in  whom  the  bile  ducts  had  been  tied)  he  could  not  find  hippuric 
acid  after  the  benzoate  of  soda  had  been  given  by  the  mouth. 

§  A.  Vogel,  loc,  cit. 


294  Amoimt  of  Chlorides,  Sulphates  and 

maining  case,  of  doubtful  diagnosis,  of  which  I  have 
spoken  before  while  treating  of  urea,  the  chlorides  were 
estimated  on  five  following  days.  The  first  day  the 
urea  was  i8  grm.  to  21  grm.  of  chlorides,  the  second 
day  it  fell  to  17  grm.  of  urea  to  14  grm.  of  chlorides,  and 
maintained  this  proportion  through  the  rest  of  the  ob- 
servations.* I  think  the  first  day's  very  high  reading 
may  be  caused  by  some  error ;  or  perhaps  accidental 
admixture,  seeing  the  abundance  of  chloride  of  sodium 
in  the  world. 

Julius  Jacobs  in  his  three  cases  found  an  increase  in 
the  chlorides  in  nearly  all :  10*717  grm.  in  the  first, 
17-818  in  the  second,  and  i4'366  in  the  third. f  In 
Valmont's  three  cases  of  cirrhosis  with  jaundice,  the 
amount  of  chlorides  was  always  small ;  sometimes  only 
two  grammes  in  the  24  hours  being  passed.  J 

There  are  also  few  observations  upon  the  amount  of 
sulphates  excreted  in  jaundice.  Kolliker  and  Miiller 
found  in  an  artificially  jaundiced  dog  that  more  sul- 
phuric acid  was  excreted  than  in  a  sound  dog ;  a  fact 
which  seems  to  them  to  show  that  the  sulphur  of  the 
taurocholic  acid  passes  into  the  urine.  In  a  case  of 
simple  jaundice  in  a  woman,  aged  25,  they  found,  how- 
ever, the  sulphuric  acid,  as  well  as  the  urea,  dimin- 
ished.§  It  seems  doubtful,  however,  if  the  decrease  of 
the  sulphuric  acid  be  not  due  to  the  general  state  of  the 
patient.  Julius  Vogel  gives  as  evidence  of  the  state 
of  chronic  disease,  that  in  a  jaundiced  man  the  amount 
of  sulphuric  acid  excreted  in  the  24  hours  was  only 
1*4  grm. II     Ernst  Bischoff  likewise  found  the  amount 

*  Wickham  Legg,  Med.  Chir.  Trans.  1876,  Vol.  lix.  p.  149. 

f  Julius  Jacobs,  Arch.f.  path.  Anat.  1877,  Bd.  Ixix.  p.  487. 

+  Valmont,  Etude  stir  les  causes  des  variations  de  Vuree,  These  de  Paris,  1879. 

§  Kolliker  and  Miiller,  Verhandlnngen  d.  phys.-med.  Gesellschaft  in  Wi'irzburg, 
1856,  Bd.  vi.  p.  492. 

II  Neubauer  and  Vogel,  Anlcitung  zur  qual.  u.  quant.  Analyse  des  Hams,  Wies- 
baden, 1863,  p.  327. 


Phosphates  in  the  Urine  of  Jaundice.  295 

of  the  sulphates  diminished,  clearly  he  thinks,  owing  to 
the  decreased  diet.*  But  he  also  noticed  another  more 
interesting  fact.  It  is  well  known,  from  Voit's  obser- 
vations, that  the  sulphuric  acid  in  the  urine  does  not 
account  for  all  the  sulphur,  and  that  a  body  con- 
taining sulphur  is  present,  probably  derived  from  tau- 
rin.  Now  the  amount  of  sulphur,  not  oxydised,  present 
in  the  urine  of  jaundice  is  much  in  excess  of  what  is 
natural ;  and  the  amount  of  excess  is  exactly  equal  to 
the  amount  of  sulphur  in  the  faeces  which  Bischoff 
calculates  should  be  passed  during  health.  So  that 
Bischoff  is  inclined  to  think  that  the  same  amount  of 
taurin,  and  therefore  of  taurocholic  acid,  is  secreted  by 
the  liver  in  jaundice  as  in  health. 

I  have  been  able  to  find  only  a  few  observations  upon 
the  amount  of  phosphates  excreted :  von  Haxthausen 
notes  that  a  jaundiced  man,  36  years  of  age,  excreted 
as  a  mean  of  24  observations,  i"g3  grm.  of  phosphoric 
acid  in  the  24  hours  ;  the  lowest  being  i'364  grm. ;  the 
highest,  3*508  grm.  The  excretion  of  phosphates  ap- 
pears to  be  less  before  noon  than  afternoon,  and  more 
in  the  night  than  during  the  day.f  Dr.  A.  W.  Foot 
found  as  a  result  of  one  observation  upon  a  jaundiced 
woman,  that  the  amount  of  phosphoric  acid  excreted 
was  58*625  grains  in  the  24  hours. J  Julius  Jacobs  in 
one  case  found  i'i83  grm.  in  the  24  hours. § 

Except  in  cases  of  acute  yellow  atrophy,  leucin  and 
tyrosin  are  not  present  in  the  urine  of  ordinary  jaundice. 
Great  caution  should  be  used  in  asserting  that  they  are 
present  in  the  urine  in  any  case.  The  mere  finding  of 
a  sediment  in  the  urine  which  shows  under  the  micro- 

*  Ernst  Bischoff,  op.  cit.  p.  150. 

t  Von  Haxthausen,  Schmidt's  jfahrbb.  1863,  Bd.  cxx.  p.  160.  Braconnot 
(yournal  de  Cheinie  med.  1827,  t.  iii.  p.  480.)  says  he  once  found  the  phosphate  of 
lime  decreased. 

X  A.  W.  Foot,  loc.  cit. 

§  Julius  Jacobs,  Arch.f.  path.  Anat.  1877,  Bd.  Ixix.  p.  487. 


296  Casts  of  the  Renal  Tubules 

scope  crystals  like  those  of  leucin  and  tyrosin  is  no 
proof  whatever  that  these  bodies  exist  in  the  urine.* 
Chemical  tests  must  be  applied  to  the  bodies  crystallised 
out  from  the  urine,  otherwise  no  reliance  can  be  placed 
upon  the  statement  that  they  are  present. 

Buddt  MurchisonJ  and  Pouzol§  have  noticed  the 
occasional  presence  of  casts  of  the  renal  tubes  in  jaun- 
diced urine.  Nothnagel  looks  upon  their  presence  as  a 
constant  phasnomenon  in  all  cases  of  intense  jaundice, 
whatever  the  cause  may  be.  He  thinks  casts  in  the 
urine  are  more  often  present  than  itching  of  the  skin  ; 
they  are  usually  hyaline  and  are  then  not  coloured 
yellow ;  epithelial  casts  are  the  next  commonest,  and 
are  deeply  yellow  coloured  ;  very  rare  are  the  so-called 
fibrinous  casts.  In  two-thirds  of  the  cases  albumen 
was  not  found  by  the  ordinary  tests,  nor  any  of  its 
modifications.  The  cases  observed  were  catarrhal 
jaundice,  jaundice  from  gall  stones,  compression  of  duct 
by  new  growth,  pyaemia,  and  "bilious"  pneumonia. || 
Dr.  Finlayson,  in  some  observations  upon  the  presence 
of  casts  in  urine  not  containing  albumen,  says  that 
tube  casts  are  almost  invariably  found  in  marked  cases 
of  jaundice,  and  this  as  a  rule  occurs  without  albumin- 
uria,^ so  that  this  observer  agrees  with  Nothnagel.  In 
the  many  cases  in  which  I  have  carefully  looked  for 
casts,  I  have  not  been  able  once  to  find  these  bodies. 
Dr.    Finlayson    appears    to    attribute    the    presence    of 

*  A  friend  of  mine,  the  late  Dr.  C.  E.  Squarey,  well  known  for  his  experience  in 
the  analysis  of  the  urine,  was  able  to  get  abundant  evidence  with  the  microscope 
of  the  presence  of  leucin  and  tyrosin  in  nearly  all  cases  of  jaundice.  Pushing  his 
results  further,  he  got  the  same  shaped  crystals  in  all  kinds  of  urine,  diseased  and 
healthy,  but  he  was  in  no  case  able  to  produce  any  evidence  of  the  presence  of 
these  bodies  in  the  urine  of  jaundice,  or  of  any  other  disease  when  using  chemi- 
cal tests. 

f  Budd,  On  Diseases  of  the  Liver,  London,  1857,  3rd  ed.  p.  288. 

I  Murchison,  Clinical  Lectures  on  Diseases  of  the  Liver,  Lond.  1868,  p.  287. 
§  Pouzol,  Essai  sicr  Victere,  Paris,  1872,  p.  18. 

II  Nothnagel,  Dcutsch.  Arch.f.  klin.  Med.  1874,  Bd.  xii.  p.  326. 

H  Finlayson,  British  and  Foreign  Med.  Chir.  Rev.  1876,  Vol.  Ivii.  p.  184. 


in  the  Urine  of  Jaundice.  297 

casts  in  the  urine  to  the  irritation  caused  by  the  pas- 
sage of  pigment. 

Kussmaul  noted  in  a  case  of  jaundice,  supposed  to 
arise  from  gall  stones,  crystals  of  bile  pigment  within 
epithelial  cells  found  in  the  urine.  The  epithelium  was 
supposed  to  be  shed  from  the  bladder.* 

*  Kussmaul,  Wurzbiirgcr  tried.  Zeitschrift,  1863,  Bd.  iv.  p.  63. 


CHAPTER   XII. 

The  Complications  of  Jaundice. 

Wasting.  One  long-noticed  complication  of  jaundice  is 
the  wasting  and  weakness.*  Even  in  cases  of  simple 
jaundice  these  symptoms  are  early  observed.  Still  cases 
are  sometimes  seen  in  which  there  is  scarcely  any  loss 
of  flesh,  and  in  which  the  patient  feels  no  weakness  even 
when  the  disease  has  lasted  a  long  time.  The  number 
of  persons  with  jaundice,  seen  in  places  of  public 
resort,  shows  that  in  some  cases  it  cannot  be  attended 
with  any  grave  inconvenience. 

The  stoppage  of  the  flow  of  bile  into  the  intestines  is 
followed  by  different  results  according  to  diff"erent  ob- 
servers. Some  state  that  no  harm  ensues,  provided 
that  a  free  escape  of  the  bile  outside  of  the  body  be 
allowed.  Others  assert  that  bile  is  necessary  to  the 
digestion,  especially  of  fats,  and  that  if  the  course  of 
the  bile  be  diverted,  death  from  inanition  will  sooner 
or  later  take  place.  Be  the  real  state  of  affairs  as  it 
may,  it  is  of  importance  to  note  that  the  glycogenetic 
function  of  the  liver  is  abolished  within  a  few  hours 
after  the  bile  ducts  are  obstructed.f  This  affords  a 
clue  to  the  wasting  and  debility  which  accompany 
jaundice.  The  value  of  glycogen  in  all  processes  of 
growth  has  long  been  known,  and  without  the  presence 
of  glycogen  it  is  probable  that  nutrition  is  seriously 
interfered  with. 

Temperature.  The  temperature  in  jaundice  is  com- 
monly natural,  or  even  below  the  standard  of  health. 
Obstruction  to  the  passage  of  the  bile  into  the  intestine 

*  Hippocrates,  de  morbis,  Lib.  ii.  Cap.  xxxix.  Littre's  ed.  t.  vii.  p.  54. 
f  J.  Wickham   Legg,  St.  Bartholomew'' s  Hospital  Reports,  1873,  Vol.  ix.  p.  161, 
and  V.  Wittich,  Centralbl.  f.  d.  med.  Wiss.  1875.  p.  291. 


Temperature  of  Jaundice.  299 

seems  of  Itself  to  cause  no  rise  of  temperature  in  the 
body.  It  is  otherwise,  of  course,  if,  as  a  cause  of  the 
jaundice,  there  be  a  febrile  disease,  such  as  pyaemia 
or  abscess  of  the  liver. 

Rohrig  has  shown  that  after  the  injection  of  bile 
acids  into  an  animal,  the  temperature  becomes  greatly 
lowered,*  and  it  is  to  the  circulation  of  these  in  the 
blood  that  he  attributes  the  low  temperature.  It  seems 
to  me  more  reasonable  to  attribute  the  symptom  to  the 
ceasing  of  chemical  changes  in  the  liver  itself.  The 
temperature  of  the  liver  is  very  high,  higher  than  that 
of  any  gland  in  the  body,  the  liver  itself  being  the  chief 
source  of  animal  heat ;  if  the  various  processes  which 
cause  this  high  temperature  come  to  an  end  there  would 
be  at  once  a  sufficient  cause  for  the  general  tempera- 
ture of  the  body  being  lowered. 

It  is  worthy  of  note  that  if  a  disease  commonly  at- 
tended with  a  high  temperature,  such  as  pneumonia,  for 
example,  be  complicated  by  a  jaundice,  the  temperature 
no  longer  shows  the  usual  high  reading.  Sometimes 
the  temperature  shows  indeed  no  rise,  even  when  the 
disease  should  be,  from  its  kind,  of  a  markedly  febrile 
character. 

Towards  the  end  of  a  chronic  jaundice  a  sudden  rise 
in  temperature  may  be  observed,  to  as  high  as  105°  or 
106°  F.f  This  rise  in  temperature  is  always  of  imme- 
diate bad  augury,  J  and  is  often  attended  with  nervous 
symptoms,  such  as  delirium  or  coma,  and  too  often  the 
death  of  the  patient  follows  in  a  few  hours. 

The  same  rise  of  temperature  is  seen  in  icterus  gravis 
just  before  death,  and  it  may  very  likely  be  only  part 
of  that  rise  of  temperature  in  the  agony  which  De  Haen 

*  A.  Rohrig,  Arch.  d.  Heilkunde,  1863,  Bd,  iv.  pp.  392,  et  seqq. 

f  Gee,  St.  Bartholomew's  Hospital  Reports,  1869,  Vol.  v.  p.  108.  Cf.  the  case  of 
Charles  Kingsley  given  in  full  under  the  head  of  xanthelasma. 

\  Wunderlich,  Das  Verhalten  der  Eigenwdrme  in  Krankheiten,  Leipzig,  1870, 
2te  Auflage,  p.  404. 


300  Itching  in  Jmindice. 

observed,  more  than  a  hundred  years  ago,  in  disorders 
not  attended  with  jaundice.* 

Itching.  A  general  itching  of  the  skin  is  common  in 
jaundice, t  according  to  Frerichs,  in  about  a  fifth  of  the 
cases,  J  although  I  feel  disposed  to  rate  the  proportion 
much  higher.  I  have  of  late  inquired  of  all  patients 
who  were  jaundiced,  whether  they  had  suffered  from 
itching  during  the  time  that  they  were  yellow,  or  imme- 
diately before  ;  and  I  find  that  out  of  48  cases,  mostly 
grown-up  men  and  women,  that  itching,  either  general 
or  local,  had  been  felt  in  -^2)  J  ^^^^  is,  a  proportion  of 
over  68  per  cent. 

The  itching  is  usually  worse  at  night,  sometimes 
being  so  severe  that  the  patients  tear  the  skin  with 
their  nails,  and  papules,  pustules,  and  even  ulcerations, 
eczema,  or  nettle-rash,  follow.  The  sensation  of  itch- 
ing is  usually  spread  all  over  the  body,  not  confined 
to  one  particular  part,  though  sometimes  it  seems  to 
attack  the  trunk  only.     It  is  most  severe  at  night. 

The  itching  is  often  most  intense  at  the  outset  of  the 
jaundice,  and  ceases  when  the  disease  has  lasted  a  few 
days.  I  have  seen,  however,  the  itching  in  some  cases 
persist  through  the  whole  course  of  the  disease,  and 
cause  the  greatest  misery  to  the  patient,  destroying 
sleep. 

Graves  mentions  a  case  In  which  the  itching  of  the 
skin  preceded  the  jaundice  by  10  days,  and  disappeared 
as  soon  as  the  jaundice  declared  itself.§ 

He  speaks  also  of  a  case  very  like  this  in  the  disap- 
pearance of  the  itching  when  the  jaundice  set  in  ;  but 
the   itching  had   persisted   for  two   months  before  the 

*  Anton,  de  Haen,  Rat.  Med.  Vindobonje,  1759,  Pars  iv.  Caput  vi.  p.  211. 

f  Hippocrates  had  already  noticed  this  symptom.  {De  morbis  internis,  Cap. 
xxxvi.  Littre's  edition,  t.  vii.  p.  256.) 

+   Frerichs,  op.  cit.  Bd.  i.  p.  113. 

§  Graves,  Clinical  Lectures  on  the  Practice  of  Medicine,  Dublin,  1864,  second 
edition,  edited  by  Neligan,  p.  637. 


Itching  in  Jaundice,  301 

jaundice  came  on.  It  is  quite  possible  that  the  two 
cases  may  be  nothing  more  than  coincidences.  Graves 
thinks  that  they  effectually  disprove  the  current  opinion 
that  the  itching  depends  upon  the  presence  of  bile  in 
the  skin.  Dr.  Austin  Flint  describes  a  case,  also  in  an 
Irishman,  where  the  itching  came  on  about  two  months 
before  the  jaundice,  and  was  accompanied  apparently 
by  urticaria.*  In  one  of  my  own  cases,  a  girl  of  14, 
the  itching  come  on  six  weeks  before  the  yellowness 
was  observed. 

That  the  itching  of  jaundice  is  sometimes  attended 
by  nettle-rash  was  noticed  by  Joseph  Frank. |  Graves 
speaks  of  cases  of  jaundice  preceded  by  inflammation 
of  the  joints,  in  which  he  was  able  to  foretell  the  ap- 
pearance of  the  urticaria.  He  looks  upon  this  sequence 
as  invariable  :  inflammation  of  the  joints,  jaundice,  urti- 
caria.J  In  a  case  noticed  by  Horaczek,  the  urticaria, 
with  dyspeptic  symptoms,  seems  to  have  slightly  pre- 
ceded the  jaundice. § 

It  is  not  known  to  what  cause  this  itching  of  the  skin 
is  due.  As  already  mentioned,  it  is  thought  by  some  to 
be  owing  to  the  presence  of  the  elements  of  the  bile  in 
the  blood.  Leyden  thinks  it  caused,  not  by  the  inert 
bile  pigment,  but  by  the  acids  ;  the  fluids  of  the  tissues 
containing  a  certain  amount  of  these,  cause  an  irrita- 
tion of  the  ends  of  the  sensory  nerves  in  the  skin,  and 
thus  cause  the  itching  felt  by  the  patients. ||  If  this 
theory  be  true,  it  would  be  interesting  to  know  if  the 
urine  contain,  at  the  beginning  of  an  attack  of  jaundice, 
a  larger  amount  of  the  bile  acids  than  later  on  in  the 
disease. 


*  Austin  Flint,  Philadelph.  Med.  Times,  1878,  Vol.  viii.  p.  507. 

•|-  Joseph  Frank,  Prax.  med.  univ.  prcec.  Lipsise,  1843,  Pars  iii.  Vol.  ii.  Sect.  ii. 
Fascic.  i.  p.  279.  Cf.  Bamberger,  Khten.  d.  chyl.  Systems,  Erlang.  1864,  2te  Aufl. 
p.  472. 

X  Graves,  op.  cit.  p.  339. 

§  Horaczek,  Die  gallige  Dyscyasic,  Wien,  1843,  p.  141. 

II  Leyden,  Beiirdge  ziir  Pathologic  des  Icterus,  Berlin,  1866,  p.  io5. 


302  The  Slow  Pulse  of  Jaundice. 

Henle  suggests  on  the  other  hand  that  the  itching 
may  be  caused  by  some  fatty  change  in  the  secretion  of 
the  skin  or  by  a  more  abundant  desquamation  of  the 
epidermis.* 

Budd  looks  upon  itching  as  one  of  the  aids  to  a  diag- 
nosis between  jaundice  from  suppression  and  obstruc- 
tion, as  itching  is  common  in  the  latter,  not  in  the 
former.f  The  same  idea  is  supported  by  Gubler,  who 
makes  the  like  distinction  between  his  ictere  bilipheique 
and  ictere  hemapheique.X 

Dr.  Murchison  says  that  boils  and  carbuncles  are 
seen  in  some  cases  of  jaundice.  §  Frerichs  speaks  of  a 
case  in  which  the  skin  was  covered  with  ring-shaped 
patches  like  urticaria.  They  did  not  however  cause 
any  inconvenience,  and  disappeared  eight  days  after 
they  were  first  noticed. ||  They  could  not  thus  have 
been  xanthelasma. 

Slow  Pulse.  It  has  been  known  for  many  years  past 
that  jaundice  is  often  accompanied  by  a  slow  pulse,  if 
the  patient  be  free  from  fever.  I  am  not  able  to  say 
precisely  who  was  the  first  to  speak  of  this  symptom. 
Galen  describes  the  pulse  in  jaundice  as  smaller,  harder, 
firmer,  not  weak,  nor  quick. 5f  The  slow  pulse  is 
spoken  of  shortly  by  Corp  ;**  John  Andree  certainly 
describes  it  and  a  case  in  which  Dr.  Hunter  found  it  as 
low  as  37. tt  Portal  likewise  mentions  the  symptom. J:{: 
It  is  only,   however,   of  late  years  that   an    attempt  to 

*  Henle,  Handb.  d.  rat.  Path.  Braunschweig,  1847,  ^^-  "•  P-  205. 

f  Budd,  op.  cit.  p.  287. 

J  Gubler,  in  Laborde,  Phys.  path,  de  Victere,  These  de  Paris,  i86g,  p.  gi. 

§  Murchison,  Clinical  Lectures  on  Diseases  of  the  Liver,  London,  1868,  p.  291. 

II  Frerichs,  op.  cit.  Bd.  i.  p.  114. 

IT  Galen,  de  pulsibus,  Lipsise,  1824,  Kiihn's  ed.  Vol.  viii.  p.  491. 

**  Corp,  An  Essay  on  the  jfaundicc,  Bath,  1785,  p.  14. 

f  f  John  Andree,  Considerations  on  Bilious  Diseases,  Hertford,  1788,  p.  39,   note. 

++  Portal,  Obs.  sur  la  nature  et  le  traitcment  des  maladies  du  foie,  Paris,  1813, 
p.  134.  It  will  be  thus  seen  that  Pouzol  {Essai  sur  Victere,  Paris,  1872,  p.  74.)  was 
quite  wrong  when  he  said  that  Bouillaud  (Traite  de  Nosographie  med.  Paris,  1846, 
t.  iii.  p.  303.)  was  the  first  to  notice  the  slow  pulse. 


The  Slow  Pulse  of  Jaundice.  303 

explain  this  phasnomenon  has  been  made.  Rohrig  first, 
in  1863,  found  that  the  injection  of  the  bile  acids  into 
the  circulation,  not  of  pigment  nor  of  cholestearin,  was 
followed  by  a  slow  pulse.  He  went  further  and  formed 
an  opinion  that  the  slow  pulse  was  due  to  the  action  of 
the  bile  acids  upon  the  ganglia  of  the  heart,  because  the 
pulse  became  slow  even  if  the  vagi  were  cut  and 
because  the  heart  of  the  frog  when  immersed  in  serum 
and  bile  acids  beat  more  slowly  than  when  immersed  in 
serum  only.*  These  reasons  would  not  now  be  ac- 
cepted by  physiologists  as  conclusive. 

Traube  in  the  following  year  published  an  explanation 
upon  altogether  different  grounds.  This  is  based  upon 
the  well-known  fact  that  the  bile  acids  rapidly  dissolve 
the  red  corpuscles  of  the  blood.  The  bile  acids,  there- 
fore, when  injected  into  the  jugular  vein,  destroy  a  large 
number  of  the  red  corpusles  and  render  that  part  of 
the  blood  unable  properly  to  exchange  oxygen.  This 
damaged  part  of  the  blood  is  rapidly  sent  through  the 
lungs  and  brought  to  the  left  side  of  the  heart,  and 
thence  carried  into  the  coronary  arteries  of  the  heart. 
The  muscular  walls,  being  thus  fed  with  blood  quite  unfit 
for  their  nourishment,  become  unable  to  contract,  and  a 
slow  pulse  follows.  This  theory  accounts  for  the  rapid 
disappearance  of  the  slow  pulse  when  once  the  injection 
has  been  ended. f  Johannes  Ranke  likewise  has  ex- 
pressed his  belief  in  the  muscular  origin  of  the  slow  pulse. 
He  found  that  when  the  bile  acids  were  injected  into  the 
aorta  of  frogs,  the  muscles  became  hard  and  rigid,  and 
did  not  answer  to  the  electrical  stimulus.  From  this  he 
concludes  that  the  striped  muscles  alone  are  concerned 
in  the  slow  pulse  of  jaundice.  J 

*  Rohrig,  Arch,  f.  Heilkunde,  1863,  p.  385.  Also  in  an  Inaugural  Dissertation, 
Ueber  den  Einfluss  der  Galle  auf  die  Herzthdtigkeit,  Leipzig,  1863. 

f  Traube,  Berliner  klin.  Wochenschrift,  1864,  p.  86 ;  also  in  Gesammelte  Beit- 
rage,  Berlin,  1871,  Bd.  i.  p.  366. 

X  Johannes  Ranke,  Arch.  f.  Anat.  u.  Phys,  1864,  p.  340:  also  in  Tetanus, 
Leipzig,  1865,  p.  395. 


304  The  Slow  Pulse  in  Jaundice. 

I  have  published  quite  a  different  explanation  of  the 
slow  pulse.*  Johannes  Ranke's  theory  must,  I  think, 
be  rejected.  It  is  quite  true  that  the  bile  acids  do 
cause  the  muscles  to  become  hard  and  not  to  answer  to 
the  electrical  stimulus,  but  this  is  due  rather  to  a  chem- 
ical than  a  physiological  action.  The  bile  acids,  even 
in  weak  solution,  coagulate  albumen,  and  if  they  be 
injected  immediately  into  the  muscles,  it  is  not  sur- 
prising that  these  should  become  hard  from  the  coagula- 
tion of  the  myosin,  and  lose  all  physiological  properties. 
If,  however,  the  bile  acids  be  injected  under  the  skin  so 
that  they  may  act  on  the  muscles  by  a  natural  process 
of  absorption,  no  change  is  seen  in  their  powers  of  con- 
traction. The  curves  traced  by  the  myograph  remain 
natural,  no  matter  how  large  the  dose  of  bile  acids. 
On  these  grounds  it  will  be  impossible  to  attribute  the 
slow  pulse  in  jaundice  to  the  failure  of  the  muscular 
walls  of  the  heart  alone.  Traube's  theory,  likewise, 
however  ingenious,  wants  a  basis  of  fact  and  must  be 
rejected. 

Nor  is  the  pulse  due  to  an  excitement  of  the  inhibi- 
tory function  of  the  vagus :  for  if  this  be  removed  by  a 
small  dose  of  atropin,  the  slow  pulse  still  arises  when 
the  bile  acids  are  introduced  into  the  circulation. 

There  remains,  therefore,  only  one  other  factor  in 
the  movements  of  the  heart,  the  ganglia ;  and  if  it  be 
safe  to  argue  in  this  case,  per  viam  exclusionis,  these 
should  be  the  means  by  which  the  slow  pulse  of  jaun- 
dice is  caused.  When  the  ganglia  are  separated  from 
the  ventricles  by  a  ligature,  no  change  follows  in  the 
alternate  rest  and  action  of  the  ventricle  when  the  bile 
acids  are  introduced  into  it.f 

The  slow  pulse  is  by  no  means  common  in  jaundice  ; 

*  Wickham  Legg,  Proceedings  of  the  Royal  Society,  1876,  Vol.  xxiv.  p.  442. 
f  For  a  fuller  account,  see  the  chapter  on  the  physiological  action  of  the  bile, 
p.  201  of  this  work. 


The  Slow  Pulse  in  Jaundice.  305 

even  in  cases  where  the  temperature  is  natural,  the 
pulse  usually  preserves  the  natural  number  of  beats.* 
When  the  pulse  is  lowered,  it  does  not  usually  fall  very 
much,  the  beats  sinking  to  70  or  60,  rarely  lower.  I 
have  indeed  seen  the  pulse  of  jaundiced  patients  as  low 
as  50,  and  once  only  as  low  as  40.  Frerichs  says  he  has 
seen  it  as  low  as  21  beats. f  It  is  usually  quite  regular. 
It  disappears,  as  Traube  remarked,  J  if  the  patient  get 
up  and  walk  about.  The  observation  must  therefore  be 
made  when  the  patient  is  lying  down. 

Frerichs  likewise  remarks  that  the  slow  pulse  dis- 
appears if  any  inflammatory  action  set  in  ;  and  on  the 
contrary,  if  during  the  progress  of  a  febrile  disorder 
jaundice  appear,  the  pulse  at  once  sinks  to  the  normal, 
or  below  it.§  I  have  not  met  with  any  like  instance. 
Vulpian  has  seen  the  palpitations  of  aortic  and  mitral 
disease  disappear  altogether  during  an  attack  of  simple 
jaundice.  II 

The  reason  that  the  slow  pulse  so  seldom  makes  its 
appearance  in  jaundice  would  seem  to  be  due  to  the 
small  amount  of  bile  acid  circulating  in  the  blood.  It 
will  be  shown  later  on  that  it  is  in  no  way  probable  that 
the  liver  secretes  any  large  amount  of  bile  acids  in 
cases  of  obstruction  to  the  gall  ducts,  and  this  is  borne 
out  by  the  fact  that  a  slow  pulse  in  jaundice  is  not  very 
common,  for  any  large  amount  of  bile  acids  secreted  by 

*  Henoch  remarks  that  he  has  never  seen  a  slow  pulse  in  the  jaundice  of  child- 
ren. Even  in  cases  absolutely  free  from  fever,  the  pulse  was  always  100-120.  He 
attributes  this  to  the  great  irritability  of  the  child's  nervous  system,  and  especially 
to  his  fear  of  the  physician,  which  may  make  up  for  the  depressing  influence  of  the 
bile  acids  on  the  pulse.  (Beitrdge  zur  KinderheUkimde,  Berlin,  1868,  p.  342.) 
Rehn  {Jahrh.f.  Kinderheilkunde ,  1870,  Bd.  iii.  p.  197.)  noticed  this  slow  pulse  in 
two  children,  in  an  epidemic  of  simple  jaundice.  Dr.  Hilton  Fagge  says  that  he 
has  never  seen  the  slow  pulse  out  of  simple  jaundice.  {Guy''s  Hospital  Reports, 
1875,  Vol.  XX.  third  series,  p.  157.) 

f  Frerichs,  op.  cif.  Bd.  i.  p.  116. 

J  Traube,  loc.  cit. 

§  Frerichs,  loc.  cit. 

II  Vulpian,  Lemons,  (annee  1874.)  Paris,  p.  143.  Cours  recueilli  par  A.  Paulier. 

X 


3o6  Heart  Murmurs  in  Jaundice. 

the  liver  and  again  absorbed,  would  undoubtedly  cause 
a  slow  pulse  in  every  case  of  jaundice,  as  well  as  severe 
accidents  in  other  parts  of  the  oeconomy. 

With  the  sphygmograph  the  pulse  in  jaundice  gives 
a  tracing  which  shows  a  very  oblique  up  line,  which 
rises  but  little,  but  which  is  a  long  time  in  coming  down 
to  the  abscissa.  The  polychrotism  is  very  marked.* 
Kleinpeter  thinks  there  is  some  increase  of  the  arterial 
pressure,  though  there  are  cases  in  which  the  tension  is 
decreased. t 

Gangolphe,  in  an  interesting  thesis,  has  pointed  out 
that  a  mitral  regurgitant  murmur  accompanies  many 
cases  of  jaundice,  especially  those  which  show  the  phae- 
nomena  of  a  slow  pulse.  In  all  cases  the  murmur  was 
first  noticed  while  the  pulse  was  slow  ;  and,  as  a  rule, 
the  murmur  disappeared  when  the  pulse  became  quicker. 
The  murmur  is  usually  very  soft,  not  harsh,  heard  with 
the  first  sound  at  the  apex  of  the  heart.  The  murmur 
is  only  heard  in  the  axilla  when  it  is  very  loud.  In 
some  cases  it  is  attended  by  a  murmur  at  the  base,  and 
a  murmur  in  the  larger  arteries.  The  murmur  is  in- 
termittent, and  does  not  last  after  the  jaundice  has 
disappeared,  thus  distinguishing  itself  from  organic 
murmurs. 

The  murmur  is  due  partly  to  a  slight  dilatation  of  the 
heart,  but  chiefly  to  a  paralysis  of  the  papillary  muscles, 
due  to  the  action  of  the  biliary  constituents  upon  the 
heart.  Gangolphe  points  out  that  in  some  cases  a  fatty 
degeneration  of  the  walls  of  the  heart  has  been  noticed 
in  acute  yellow  atrophy,  and  in  acute  poisoning  by  the 
bile  acids.  He  does  not  think  that  anaemia  has  any- 
thing to  do  with  these  murmurs. J 

*  Marey,  quoted  by  Straus,  dcs  Icteres  chroniqucs,  Paris,  1878,  p.  no. 
f  Kleinpeter  and  Lorain,  quoted  by  Straus. 

X  Gangolphe,  Du  bruit  de  soiiffle  mitral  dans  Victcrc,  These  de  Paris,  1875. 
For  his  general  conclusions  see  p.  41. 


Heart  Murmurs  in  Jaundice.  307 

It  is  worthy  of  note  that  in  some  of  Gangolphe's 
cases,  a  murmur  was  sometimes  developed  at  the  base 
of  the  heart  and  along  the  great  vessels,  phasnomena 
usually  associated  with  anaemia.  In  jaundice  the  red 
corpuscles  are  often  decreased  in  number,  and  the 
blood  is  in  a  watery,  poor  state  :  it  would  be  hard  to 
disbelieve  that  any  tendency  to  a  murmur  should  not 
thus  be  aggravated.  It  is,  however,  highly  probable 
that  the  murmurs  are  caused  by  the  circulation  in 
the  blood  of  the  bile  acids,  as  the  murmur  is  found 
so  constantly  associated  with  a  slow  pulse.  Other  poi- 
sons which  have  a  direct  action  upon  the  heart  some- 
times cause  a  transient  murmur,  for  my  friend  and 
colleague  Dr.  Lauder  Brunton  informs  me  that  he  has 
frequently  found  a  mitral  murmur  develope  in  dogs 
when  they  were  placed  under  the  influence  of  digitalis. 
Dr.  Brunton,  like  Gangolphe,  attributes  the  murmur  to 
an  imperfect  action  of  the  papillary  muscles. 

I  have  never  myself  seen  a  murmur  which  passed  away 
with  the  disappearance  of  the  jaundice,  though  I  have 
not  unfrequently  seen  jaundice  develope  in  persons 
already  the  subject  of  heart  disease. 

Fabre  says  that  since  the  publication  of  Gangolphe's 
thesis,  he  has  noticed  a  murmur  over  the  heart  in  five 
out  of  eight  cases  of  jaundice.  He  attributes  the  mur- 
mur to  a  myocarditis  caused  by  the  toxic  action  of  the 
bile  acids.* 

Potain  has  other  views  as  to  the  cause  of  the  murmurs 
heard  in  jaundice.  He  thinks  that  the  liver  will  be  found 
to  hold  the  same  connexion  with  heart  disease  that  the 
kidney  does,  and  that  in  diseases  of  the  liver,  especi- 
ally in  chronic  jaundice,  there  will  be  enlargement  of 
the  heart,  chiefly  of  the  right  side  ;  a  dilatation,  rather 
than  hypertrophy,  with  tricuspid  incompetence,  as  a 
result  of  the  disease  of  the  liver ;  not  I  must  own  as  we 

*  Fabre,  Gaz,  des  Hop.  1877,  p.  gi6. 

X  2 


3o8  Bitterness  of  Taste. 

are  now  accustomed  to  think,  that  the  disease  of  the 
liver,  as  nutmeg  liver,  is  secondary  to  the  tricuspid 
regurgitation.* 

Changes  in  Power  of  Perception.  In  some  cases  of 
jaundice,  the  senses  of  taste  and  sight  seem  to  suffer, 
and  to  give  wrong  intelligence  to  the  patient.  Neither 
of  these  phsenomena  is  common,  but  it  is  characteristic 
of  the  love  of  the  marvellous  that  upon  these  two  symp- 
toms, the  non-medical  mind  should  have  fastened  as 
essential. 

i.  Bitterness  of  Taste.  It  is  said  that  patients  with 
jaundice  sometimes  complain  of  a  bitter  taste  ;  and  in 
ancient  times  this  was  thought  to  be  invariable. i*  I 
have  myself  not  met  with  any  such  perversion  of  taste 
in  my  own  cases.  It  has  been  thought  to  be  due  to  the 
passage  of  bilious  matters  into  the  mouth,  J  apparently 
through  the  saliva  ;  and  the  behaviour  of  animals,  dur- 
ing the  injection  of  bile  acids  into  their  veins,  might  be 
pointed  out  in  support  of  this  view.  The  creatures 
thrust  out  their  tongues,  and  lick  their  lips  and  jaws  as 
if  to  rid  themselves  of  a  disagreeable  sensation. §  I 
should  myself  look  upon  the  gastric  state  which  accom- 
panies so  many  cases  of  simple  jaundice  as  a  more 
probable  cause  of  a  bitter  or  disagreeable  taste  rather 
than  the  circulation  of  the  bile  acids  in  the  blood,  or 
their  escape  through  the  saliva,  although  Dr„  Fenwick 
has  attempted  to  prove  that  they  may  not  uncommonly 
be  found  in  the  saliva  of  jaundice. ||  Heberden  says 
it  is  far  from  uncomm.on  to  have  all  solid  and  liquid  food 
taste  bitter ;  and  speaks  of  one  to  whom  everything 
tasted  bitter,  except  oysters.^ 

*  Potain,  reported  by  Straus,  Des  Icteres  Chroniques,  Paris,  1878,  p.  114. 
f  M.  A.  Antoninus,  Thoughts,  vi.  57,  Long's  Transl.  London,  1869,  Sec.  ed. 
p.  130.     "  To  the  jaundiced  honey  tastes  bitter." 

+  Henle,  Handb.  d.  rat.  Path.  Braunschweig,  1847,  Bd.  ii.  p.  206. 

§  See  p.  192  of  this  work. 

II  Fenwick,  Lancet,  iS-jj,  Vol.  ii.  p.  303. 

U  Heberden,  Commentaries,  Loud.  i8o5,  3rd  ed.  p.  247. 


Xanthopsy.  309 

ii.   Yellow  Vision.      In   some   rare  cases  of  jaundice, 
all,  or  only  white,  objects  appear  yellow  to  the  patient. 
The   first  account  of  this  symptom  on  record  is  given 
by  Lucretius,  a  non-medical  writer,  who  says : 
"Lurida  prseterea  fiunt  quaecomque  tuentur 
Arquati."* 

words  which  have  passed  into  a  proverb. t  Galen  likewise 
speaks  of  the  symptom,  saying  that  all  objects  are  seen 
yellow  by  the  jaundiced.  J 

Although  this  symptom  is  by  no  means  common,  yet 
Sydenham,  the  pride  and  glory  of  English  medicine, 
speaks  of  it  as  part  of  the  definition  of  jaundice,  that  all 
objects  appear  yellow. §  Mercurialis,  on  the  other  hand, 
altogether  rejects  this  appearance  as  unheard  of.|| 
There  can  be  no  doubt,  however,  of  its  occasional  ap- 
pearance. I  have  myself,  during  three  years,  met  with 
no  less  than  three  cases.  Still  many  writers  look  upon 
it  as  a  symptom  of  great  rarity.  Peter  Frank  says  that 
in  the  course  of  54  years,  he  met  with  this  symptom 
only  five  times  ;^  and  Frerichs  says  he  has  never  seen 
a  case  although  he  has  always  asked  for  the  symptom.** 

Yellow  vision  is  usually  seen  only  in  intense  jaundice, 
and  then  for  no  great  length  of  time,  for  the  symptom 
rapidly  passes  off.  I  have,  however,  seen  yellow  vision 
last  for  three  days.  As  a  rule,  only  white  objects  ap- 
pear yellow  ;  but  in  some  severe  cases  all  objects  have 
a  yellow  shimmer. 

*  Lucretius,  de  reriim  natura,  Lib.  iv.  331.  Some  think  that  Hippocrates  speaks 
of  this  symptom,  {De  locis  in  hoviine  Cap.  16)  when,  as  some  read,  it  is  said  that 
jaundice  is  dangerous  when  it  falls  upon  the  eyes.  Littre  (his  edition  of  Hipp, 
t.  vi.  p.  308.)  adopts  quite  a  different  construing. 

f  They  are  quoted  by  Montaigne  in  his  long  essay  on  natural  religion  or  apology 
for  Raymond  of  Sebonde,  {Essais,  Livre  ii.  Chap,  xii.)  to  show  how  completely  we 
are  at  the  mercy  of  our  senses.  See  also  Sextus  Empiricus,  Pyrrhon.  Hypot.  Lib.  i. 
Cap.  xiv. 

\  Galen,  De  symptom,  different.  Cap.  ii.  Kiihn's  ed.  Vol.  vii.  p.  99. 

§  Sydenham,  Processus  Integri,  Cap.  xxix.  ed.  Greenhill,  p.  582. 

II  Mercurialis,  Var.  Lect.  in  Med.  Script.  Venetiis,  1598,  Lib.  vi.  Cap.  xii.  p.  129. 

%  J.  P.  Frank,  De  curand.  horn.  morb.  epitome^  Viennas,  182 1,  Lib.  vi.  Pars  iii. 

p.  307- 

**  Frerichs,  op.  clt.  Bd.  i.  p.  115. 


310  Xanthopsy  of  Jaundice. 

The  cause  of  the  yellow  vision  is  quite  unknown. 
Many,  led  by  Morgagni,*  have  thought  it  to  be  due  to 
the  impregnation  of  the  humours  of  the  eye  by  bilious 
fluids.  Peter  Frank,  however,  objected  to  this  doctrine 
on  three  grounds:  i.  that  he  had  often  seen  the  cornea 
yellow  without  disturbance  of  vision  ;  ii.  that  the 
yellow  vision  is  often  intermitting ;  and  iii.  that  a 
woman,  suffering  from  typhoid,  who  had  never  been 
jaundiced,  saw  all  things  yellow  for  two  days.f 

He  allows  that  yellow  vision  may  sometimes  arise 
from  coloured  humours  or  membranes  of  the  eye,  yet 
he  evidently  thinks  that  the  whole  phsenomenon  may 
well  be  explained  on  nervous  grounds.  Joseph  Frank, 
following  his  father,  points  out  that  the  disorder 
is  not  unfrequently  attended  by  night  bhndness,  and 
that  it  is  very  possibly  due  to  some  changes  in  the  optic 
nerve. J  Stokes  seems  likewise  to  favour  the  view  of 
nervous  origin. § 

EUiotson,  on  the  other  hand,  made  a  return  to  the 
views  of  Morgagni.  He  found  that  one  of  his  patients 
who  was  jaundiced,  saw  yellow  with  the  left  eye,  and 
not  with  the  right ;  in  the  left,  two  large  red  vessels  ran 
over  the  cornea;  in  the  right,  there  was  no  enlargement 
of  the  vessels.  EUiotson  infers  that  the  serum  of  the 
blood  passing  in  front  of  the  eye  tinges  all  things  yellow. 
He  had  soon  after  this  another  jaundiced  patient  who 
saw  yellow,  and  in  whom  the  conjunctiva  around  the 
cornea  was  greatly  inflamed.  ||  Sir  Thomas  Watson, 
likewise,  records  the  case  of  a  patient  who  saw  yellow, 

*  Morgagni,  De  scdibus,  etc.  Ep.  xxxvii.  Art.  8.  Of.  Le  Cat,  Traite  de  la  couleur 
dc  la  peaii  hnmaine,  Amsterdam,  1765,  p.  161.  He  found  in  a  case  of  jaundice  the 
aqueous  and  vitreous  of  a  yellow  tint. 

f  J.  P.  Frank,  op.  cit.  p.  344. 

X  Joseph  Frank,  op.  cit.  p.  276.  Bamberger  (Kranhheiten  d.  chyl.  Syst.  in 
Virchow's  Handbuch,  Erlangen,  1864,  2te  Aufl.  p.  473.)  remarks  that  all  the  cases 
of  day  and  night  blindness,  which  he  has  seen  associated  with  jaundice,  have  died. 

§  Stokes,  London  Med.  and  Surg,  yournal,  1834,  Vol.  v.  p.  200. 

II  EUiotson,  Lond.  Med.  Gaz.  1833,  Vol.  xii.  p.  486. 


Daltonism  seen  in  Jaundice.  311 

and  who  had  several  varicose  and  singularly  tortuous 
vessels  proceeding  across  the  sclerotica  towards  the 
cornea,  and  some  of  them  reached  its  margin.  He 
endorses  Elliotson's  view  and  thinks  that  the  vessels 
when  enlarged  by  disease,  give  a  passage  to  the  yellow 
colouring  matter,  so  that  all  things  appear  as  if  viewed 
through  yellow  stained  glass.*  Dr.  Murchison  records 
a  case  of  yellow  vision,  in  which  the  conjunctival  ves- 
sels were  large  both  during  and  after  the  yellowness  of 
sight. t 

Rose  has  supported  Peter  Frank's  theory  of  a  nerv- 
ous cause  for  the  yellow  vision.  In  one  of  his  cases  he 
found  a  marked  Daltonism,  an  inability  to  distinguish 
red,  as  well  as  a  seeing  of  objects  yellow.  He  found 
the  humours  of  the  eye  very  imperfectly  coloured  and 
dismisses  these  as  a  cause  of  the  yellow  vision. J  Un- 
fortunately in  this  case  it  was  impossible  to  ascertain 
if  the  Daltonism  existed  in  health.  Santonin  seems  to 
cause  a  like  yellow  vision  and  a  like  Daltonism.  The 
phaenomena  of  the  two  may  be  profitably  compared 
together. 

During  the  last  three  years  I  have  met  with  three  cases 
of  yellow  vision  in  jaundice.  Like  Heberden's  cases 
they  have  all  been  women. §  In  one  case  an  old  woman 
aged  66  was  examined  with  the  ophthalmoscope.  The 
beginnings  of  cataract  hindered  the  disc  of  the  left  eye 
from  being  seen  ;  in  the  right  the  disc  was  somewhat 
pink.  Nothing  else  unnatural  was  seen.  There  were 
no  enlarged  vessels.  The  skin  was  intensely  jaundiced, 
the  stools  colourless ;  the  liver  stretched  two  fingers' 
breadth  below  the  margin  of  the   ribs.       Only   white 

*  Thomas  Watson,  Lectures  on  the  Principles  and  Practice  of  Physic,  Lond. 
1857,  Vol.  ii.  p.  605. 

+  Murchison,  Clinical  Lectures  on  Diseases  of  the  Liver,  London,  1868,  p.  295. 

X  Rose,  Arch.  f.  path.  Anat.  1864,  Bd.  xxx.  p.  442.  Dr.  Moxon  {Lancet,  1873, 
Vol.  i.  p.  130)  examined  7  cases  of  jaundice  in  which  there  was  no  xanthopsy,  and 
found  the  humours  of  the  eye  perfectly  colourless. 

§  Heberden,  Commentaries,  London,  1806,  Third  ed.  p.  242. 


312  HcBinorrhagic  Diathesis. 

things  were   noticed  to  be  yellow.      She   died  shortly 
afterwards  in  her  own  home. 

In  a  short  research  which  was  conducted  by  Dr. 
Vincent  Harris  and  m3'self,  the  power  to  judge  of  col- 
ours was  tested,  without  beforehand  asking  the  patient 
if  he  saw  yellow.  15  patients,  suffering  from  jaundice 
due  to  various  causes,  were  examined  on  the  following 
plan :  a  sheet  of  paper  upon  which  were  painted  many 
of  the  various  shades  of  the  primary  colours  was  pre- 
sented to  the  patient,  and  he  was  desired  to  name  the 
colours  as  they  were  pointed  out.  Particular  attention 
was  directed  to  the  judging  aright  of  blue,  green,  and 
red.  In  every  case,  save  two,  perfectly  correct  answers 
were  given,  even  to  minute  shades  of  colour.  One  of 
these  was  an  old  Irishwoman,  and  we  put  little  trust  in 
what  she  told  us.  The  second  was  a  man,  aged  21,  with 
simple  jaundice,  who  persisted  in  stating  that  green  was 
yellow.  After  this  they  were  all  examined  with  Rose's 
instrument*  to  test  their  Daltonism  ;  but  with  this,  no 
change  was  noted.  The  patients  were  likewise  ex- 
amined with  the  ophthalmoscope  with  a  negative  re- 
sult, t 

Since  the  publication  of  Stilling's  sheets  for  testing 
eyes,  I  have  used  them  in  every  case  of  jaundice  that 
I  have  met  with,  but  I  have  seen  no  loss  of  power  in 
detecting  at  once  the  various  figures  and  letters. 

HcBinorrhagic  Diathesis.  In  some  acute  forms  of 
jaundice,  and  in  chronic  jaundice  which  has  lasted  for 
a  long  time  and  draws  towards  its  end,  haemorrhages 
from  the  mucous  membranes  and  under  the  skin  are 
far  from  uncommon. 

I  do  not  know  if  the  short  account  given  by  Hippo- 
crates himself  of  certain  persons  who  became  jaundiced 

*  For  an  account  of  this,  see  Rose's  paper  in  Arch.  f.  path.  Anat.  1863,  Vol. 
xxviii.  p.  35. 

t  Wickham  Legg  and  Vincent  Harris,  St.  Bartholomew'' s  Hospital  Reports, 
1876,  Vol.  xii.  p.  167. 


Hcemorrhagic  Diathesis.  313 

during  the  course  of  a  fever,  but  who  were  relieved  by 
an  abundant  haemorrhage,  may  be  looked  upon  as  some 
description  of  the  hsemorrhagic  diathesis  in  jaundice.* 
Huxham  speaks  at  length  of  the  haemorrhagic  diathesis 
in  jaundice,  saying  that  the  haemorrhages  are  not 
uncommon  in  the  more  severe  kinds  of  jaundice,  and 
that  the  blood  comes  forth  from  all  the  openings  of  the 
body,  and  that  the  bleedings  yield  to  no  remedies. f 
Richard  Bright,  in  his  valuable  papers  on  jaundice, 
notices  that,  at  the  end  of  the  disease  the  patient  be- 
comes drowsy,  ecchymosis  takes  place  in  various  parts, 
and  blood  escapes  from  different  surfaces.  In  the  more 
active  and  febrile  forms,  he  says,  this  haemorrhagic  ten- 
dency may  come  on  very  early  and  be  excessive.  J  The 
appearance  of  a  haemorrhagic  diathesis  has  likewise  been 
noted  by  Budd,§  Bamberger,  ||  Leyden,5[  Murchison,** 
and  others ;  it  has  been  made  the  subject  of  an  essay 
by  Monneretft  and  Laugier,{J  and  numerous  single 
cases  will  be  found  scattered  through  the  journals. 

The  haemorrhagic  diathesis  is  seen  very  markedly  in 
the  jaundice  which  accompanies  acute  yellow  atrophy 
of  the  liver.  It  will  be  fully  described  hereafter.  In 
chronic  jaundice  the  haemorrhages  rarely  appear  save 

*  Hippocrates,  Epidem.  liber  i.  Cap.  viii.  Littre's  ed.  t.  ii.  p.  642.  Haemor- 
rhages in  diseases  of  the  liver  were  certainly  noted  by  Hippocrates  {Prognostic. 
Cap.  vii.  Littre's  ed.  t.  ii.  p.  126.) 

f  Huxham,  Obs.  de  Aere,  etc.  Londin.  1739,  p.  142.  The  very  words  of  Huxham 
are  quoted  by  Joseph  Frank  {Prax.  nied.  univ.  prcec.  Lips.  1843,  Pars  iii.  Vol.ii.  Sect, 
ii.  p.  314,  note)  as  those  of  Forestus,  a  writer  of  the  latter  half  of  the  seventeenth 
century.  I  have  tried  to  verify  the  reference  {Obs.  et  cur.  med.  et  chir.  op.  omnia, 
Rothomagi,  1653,  Lib.  xix.)  given  by  Frank,  but  have  failed. 

J  Bright,  Guy's  Hospital  Reports,  1836,  Vol.  i.  p.  614. 

§  Budd,  On  Diseases  of  the  Liver,  London,  1857,  S^d  edit.  pp.  228  and  473. 

II  Bamberger,  Krankheiten  d.  chylopoetischen  Systems,  Erlangen,  1864,  2te.  Au- 
flage,  p.  584. 

IT  Leyden,  Beitrdge  ziir  Path.  d.  Icterns,  Berlin,  1866,  p.  108. 

**  Murchison,  Clinical  Lectures  on  Diseases  of  the  Liver,  London,  1868,  p.  294. 

f  f  Monneret,  Arch.  gen.  de  Med.  1854.  Vol.  i.  p.  641. 

XX  Laugier,  Dcs  hemorrhagies  liees  an  retrecissement  dcs  votes  biliaires.  These  de 
Paris,  1870. 


314  Hcemorrhagic  Diathesis. 

towards  the  end  of  the  patient's  Hfe ;  they  are  of 
a  very  grave,  if  not  fatal,  significance.  Epistaxis  is 
an  extremely  common  form  of  haemorrhage,  and  the 
bleeding  is  often  very  abundant.  Hsematemesis  and 
haemorrhage  from  the  bowel  are  also  very  common. 
Hsematuria  is  not  nearly  so  common,  but  it  has  been 
seen*  and  also  traumatic  haemorrhages,  as  from  leech 
bites. t  Petechiae  are  often  seen  on  the  skin,  and  after 
death  on  the  serous  membranes.  The  gums  and  con- 
junctiva sometimes  bleed  and  show  petechiae. 

The  amount  of  blood  lost  may  be  so  great  as  to  cause 
death.  The  bleedings  may  begin  several  months  before 
deathj  and  continue  with  intermissions  till  the  patient 
either  die  of  the  bleedings,  or  of  the  cause  of  the  jaun- 
dice. 

Haemorrhages  have  likewise  been  seen  in  the  men- 
inges of  the  brain  and  the  ventricles. §  Floodings  are 
sometimes  seen  ;  and  haemorrhages  into  the  ovary,  into 
the  muscles,  in  fact  into  every  part  of  the  body. 

Haemorrhages  in  chronic,  as  well  as  in  acute  jaundice 
are  more  common  into  the  stomach  and  intestine  than 
into  other  parts,  if  epistaxis  be  excluded.  In  chronic 
jaundice,  this  may  be  explained  by  the  disturbance  in 
the  circulation  of  the  liver,  a  theory  adopted  by  Budd. 
In  icterus  gravis  it  is  not  so  easy  of  solution. 

The  cause  of  these  haemorrhages  in  chronic  jaundice 
is  obscure.  It  is  not  merely  the  marasmus  which 
accompanies  the  disorder,  as  the  haemorrhages  are  seen 
in  acute  jaundice,  or  the  impoverished  state  of  the 
blood,  as  Budd  supposes,  ||  but  it  seems  to  be  the  jaun- 
dice   itself,    that    is  the  bile    circulating  in  the    blood, 

*  Laugier,  op.  cit.  p.  11.     Monneret,  loc.  cit. 

f  Laugier,  op.  cit.  p.  16.     Mettenheimer,  Beitragc  zti  der  Lchre  von  den  Grciscn- 
krankheitcn,  Leipzig,  1863,  p.  120. 
X  Laugier,  op.  cit.  p.  19. 
§  Reclus,  Gaz.  des  Hop.  1872,  p.  260. 
II  Budd,  op.  cit.  p.  473. 


Hcsmorrhagic  Diathesis.  315 

which  is  the  source  of  the  haemorrhage.  Of  the  ele- 
ments of  the  bile,  the  only  one  known  to  possess  any 
power  of  begetting  haemorrhages  is  the  bile  acids,  and 
it  is  to  the  action  of  the  bile  acids  upon  the  blood  cor- 
puscles that  Leyden  seems  inclined  to  attribute  the 
phaenomena.*  Were  this  the  case,  haematuria  ought  to 
be  a  constant  accompaniment  of  the  haemorrhagic  dia- 
thesis, just  as  it  is  always  seen  after  the  injection  of 
bile  acids  into  the  circulation  ;  a  large  amount  of  hae- 
moglobin being  set  free  in  the  plasma  of  the  blood  and 
thrown  out  by  the  kidneys. 

It  is  most  in  accordance  with  the  present  state  of 
knowledge  to  believe  that  haemorrhages  are  preceded 
by  a  diseased  state  of  the  blood  vessels,  and  it  is  to  the 
state  of  blood  vessels  rather  than  to  the  state  of  the 
blood  that  haemorrhages  are  due.  If  this  be  granted, 
it  will  be  necessary  to  search  for  some  cause  of  disease 
of  the  blood  vessels  in  chronic  jaundice.  Leyden  has 
shown  that  the  bile  acids  cause  a  parenchymatous  de- 
generation, not  only  of  the  glands,  but  also  of  the 
muscles. f  If  the  middle  coat  of  the  arteries  share  in 
this  degeneration,  a  sufficient  cause  of  haemorrhages  is 
set  up.  It  will  be  interesting  to  watch,  as  opportunity 
offers,  for  evidence  of  an  extensive  degeneration  of  the 
vessels  in  cases  of  haemorrhage  in  jaundice,  such  as 
very  probably  exists  in  all  cases  of  icterus  gravis. 

A  curious  haemorrhagic  diathesis  often  attended  by 
jaundice  is  seen  in  the  umbilical  haemorrhage  of  the 
new-born.  Out  of  220  cases  which  Grandidier  has  col- 
lected, jaundice  was  present  in  84  ;  in  35,  jaundice  and 
ecchymoses  were  seen  together,  and  this  appears  to  be 
a  most  serious  complication,  for  out  of  the  35  only  3 
recovered. J 

*  Leyden,  loc.  cit. 
f  Leyden,  op.  cit.  p.  loo. 

X  GTcLndidiGT,  Die  freiwilligen  Nabelbhitungen  der  Neugeborenen,  Cassel,  1871, 
p.  62. 


3i6  Nervous  Symptoms, 

When  haemorrhages  set  in  during  the  progress  of  a 
case  of  jaundice,  the  prognosis  becomes  very  grave,  but 
not,  as  Laugier  asserts,  altogether  fatal.  Monneret  and 
other  v/riters  have  recorded  cases  of  recovery  after  epis- 
taxis  and  even  petechise.*  There  are  also  cases  on 
record  of  recovery,  even  when  a  hsemorrhagic  diathesis 
has  set  in  in  cases  of  umbilical  haemorrhage  compli- 
cated with  jaundice.  Frankelf  has  published  the  notes 
of  a  very  interesting  case.  A  man,  aged  31,  during  the 
course  of  a  simple  jaundice  was  attacked  by  hcema- 
temesis  and  haemorrhage  from  the  bowel.  He  re- 
covered quickly  from  the  jaundice  after  haemorrhage 
had  ceased ;  the  day  after  the  haemorrhage  had  stopped 
the  urea  passed  in  24  hours,  rose  from  10  grammes  to 
42'i7.  The  chlorides  during  the  highest  reading  of  the 
urea  were  small  in  amount,  but  rose  as  the  urea  fell. 
The  rise  in  the  urea  after  haemorrhage  is  known. 

Nervous  Symptoms.  In  nearly  all  cases  of  icterus 
gravis,  and  in  most  cases  of  chronic  jaundice  just  before 
death,  delirium  and  coma,  and  sometimes  convulsions, 
set  in.J  In  some  cases  the  appearance  of  the  nervous 
symptoms  is  attended  by  a  rise  of  temperature. 

The  cause  of  these  phaenomena  and  the  various 
theories  which  labour  to  explain  them  will  be  best  fully 
discussed  under  the  head  of  icterus  gravis.  It  may  here 
be  stated  that  many  authors  believe  them  to  be  due  to 
a  circulation  of  the  bile  elements  in  the  blood,  a  cho- 
Isemia,    while     others     attribute    them    to    a    uraemia. 

*  Monneret,  Arch.  gen.  de  Med.  1854,  Vol.  i.  p.  641,  and  de  Victere  hem.  ess. 
Paris,  1859,  p.  14,  from  yournal  de  Progres. 

f  Frankel,  Charite-Annalen,  1876,  Bd.  iii.  Berlin,  1878,  p.  292. 

\  Hippocrates  has  said  :  xockov  Vi  W)  Ikt'i^oj  (/.ufoura  {Praen.  Coacae  vi.  194.  Littre's 
ed.  t.  V.  p.  626.)  but  in  modern  times  Bamberger  {Krankheitcn  d.  chyl.-po'ct.  Systems, 
Erlangen  1864,  ate  Auft.  p.  473.)  was,  I  believe,  the  first  to  point  out  how  common 
the  nervous  symptoms  are  at  the  end  of  chronic  jaundice.  My  own  experience 
is  completely  in  accordance  with  that  of  Bamberger's.  Bright  [Guy's  Hosp.  Re- 
ports, 1836,  Vol.  i.  p.  609.)  says  that  the  patient  becomes  drowsy  in  the  last  stage  of 
jaundice,  and  that  (p.  614)  when  the  disease  is  more  acute  and  febrile,  the  nerv- 
ous symptoms  come  on  early. 


Xanthelasma.  317 

Schonlein  strangely  attributes  the  delirium  to  the  de- 
posit of  bile  pigment  in  the  membranes  of  the  brain.* 

In  nearly  all  cases  of  jaundice,  although  there  may 
be  no  marked  brain  symptoms,  as  delirium,  &c.  yet 
there  seems  a  change  of  humour  if  the  patients  become 
fretful  and  peevish.  They  are  disposed  to  sleep  and 
indisposed  to  any  mental  exertion. 

Xanthelasma.  After  jaundice  has  lasted  for  some 
months,  there  appear,  now  and  then,  upon  the  eyelids, 
small,  oval  or  rounded,  symmetrical  patches  of  the 
colour  and  appearance  of  chamois  leather,  now  called, 
by  the  greater  number  of  observers,  xanthelasma. J 
Xanthelasma  palpebrarum  is  seen  in  other  diseases 
besides  jaundice.  Dr.  Church  has  shown  its  heredi- 
tary character, §  and  Mr.  Hutchinson,  who  has  made  a 
great  study  of  this  disorder,  has  pointed  out  its  con- 
nexion with  the  state  called  by  the  older  physicians  the 
"bilious  state;"  that  is,  headache  and  vomiting;  the 
seat  of  the  bilious  state  being  the  stomach,  not  the 
liver.  Xanthelasma  has  also  been  seen  in  diabetes ; 
but  there  seems  no  good  grounds  for  associating  xanthe- 
lasma with  any  special  morbid  state  save  jaundice.  || 

Rayer  seems  to  have  been  the  first  to  describe  and 
figure  xanthelasma  ]%    the   patient    does  not   seem  to 

*  Schonlein,  Klinische  Vortrage,  Berlin,  1842,  p.  311. 

f  Hippocrates  speaks  of  the  great  irritability  of  temper  in  the  jaundiced.  (De 
aff.  int.  cap.  xxxv.  Littre's  ed.  t.  vii.  p.  252.)  I  cannot,  however,  think  that  he 
referred  to  the  delirium  of  jaundice  in  the  passage  where  he  distinguished  between 
the  effect  of  bile  and  phlegm.  Those  who  become  mad  from  phlegm  are  quiet, 
do  not  cry  out  and  are  not  agitated ;  but  those  who  become  mad  from  bile  cry  out, 
are  mischievous,  and  always  in  movement.  (De  morbo  sacro,  cap.  xv.  Littre's  ed. 
t.  vi.  p.  389.  Cf.  Democrit.  epist.  t.  ix.  p.  385.)  It  seems  to  me  that  jaundice 
is  not  spoken  of,  but  that  madness  is  explained  on  the  old  humoral  pathology. 

X  This  name  was  first  proposed  by  Mr.  Erasmus  Wilson  (On  diseases  of  the  skin, 
Lond.  6th  ed.  1867,  p.  773.)  It  is  derived  from  ^a,vSis,  yellow,  and  iXafffta..,  metal 
beaten  out. 

§  W.  S.  Church,  St.  Bartholomew'' s  Hospital  Reports,  1874,  Vol.  x.  p.  65. 

II  Hutchinson,  Med.  Chir.  Trans.  1871,  Vol.  liv.  p.  171. 

*  Rayer,  Traite  des  Maladies  de  la  Peau,  Paris,  1835,  2e.  ed.  Atlas,  pi.  xxii.  fig. 
15.     The  young  man  spoken  of  by  Portal,  {Maladies  dii  Foie,  Paris,  1813,  p.  121.) 


3i8  Causes  of  Xanthelasma. 

have  been  jaundiced.  The  disease  was  afterwards 
named  vitiHgoidea  by  Addison  and  Gull.*  Within  the 
last  lo  years  the  disease  has  drawn  a  great  deal  of 
attention  both  in  England  and  in  Germany,  Dr. 
Murchisonf  and  WaldeyerJ  being  the  first  to  point 
out  the  true  histological  characters  of  the  spots. 

Besides  the  names  of  xanthelasma  and  vitiligoidea, 
this  appearance  has  been  likewise  called  xanthoma  by 
Frank  Smith, §  a  term  adopted  by  Kaposi.  ||  Virchow  has 
proposed  to  call  it  Fibroma  lipoinatodes,%  a  name  which 
does  not  seem  to  have  been  followed  by  anyone,  and 
against  which  Dr.  Pye-Smith  has  with  great  justice 
protested.**  Stearrhcea  ftavescens  and  molluscum  choles- 
teriqiie  are  other  names  which  it  is  to  be  hoped  will 
(in  like  manner)  be  soon  forgotten. 

Xanthelasma  is  not  caused  save  by  a  long  continu- 
ance of  the  jaundice.  The  shortest  time  in  which  I 
have  seen  it  arise  is  six  months  after  the  first  onset  of 
the  jaundice,  and  Dr.  Pye-Smith  in  less  than  four.J:|: 
It  is,  however,  rarely  seen  earlier  than  twelve  months. 
It  does  not  seem  to  be  needful  that  the  jaundice  should 
be  intense,  but  that  it  should  be  continuous  ;  and  what, 
in  cases  of  jaundice,  determines  the  xanthelasma  is 
quite  unknown.  It  is  not  dependent  on  the  variety  of 
jaundice,  as  Mr.  Hutchinson  thought  probable, §§  the 
disease   being   seen   with    a   small    amount    of  icteric 

who  suffered  from  jaundice  for  three  years,  and  was  then  attacked  by  tubercles  or 
a  sort  of  wart  on  the  back  and  legs  probably  had  xanthelasma. 

*  Addison  and  Gull,  Guy's  Hospital  Reports,  1851,  Series  ii.  Vol.  vii.  p.  265. 

f  Murchison,  Trans,  of  the  Path.  Soc.  of  London,  i86g.  Vol.  xx.  p.  187. 

J  Waldeyer  and  Jany,  Sitzbb.  d.  schles.  Gcscll.f.  vatcrland.  Cultur,  Juli,  1S68, 
quoted  in  Virchow's  Jahrcsbf.  1869,  Bd.  ii.  p.  548. 

§  W.  F.  Smith,  Journal  of  Cutaneous  Medicine,  London,  1869,  Vol.  iii.  p.  241. 

II  Kaposi,  Hautkrankheiten,  Stuttgart,  2te  Auflage  1876,  Bd.  ii.  p.  251.  in 
Virchow's  Handb.  d.  spec.  Path,  und  Ther.  Bd.  iii.  Abth.  ii. 

11  Virchow,  Arch. f.  path.  Anat.  1871,  Bd.  Iii.  p.  508. 

••  Pye-Smith,  Guy's  Hospital  Reports,  1877.  p.  113. 

IX  Pye-Smith,  op.  cit.  p.  127. 

§§  Hutchinson,  op.  cit.  p.  iSr. 


Causes  of  Xanthelasma.  319 

staining  and  bilious  stools,  as  well  as  with  the  severe 
melasicterus.  Nor  is  xanthelasma  associated  with  any 
peculiar  disease  of  the  liver ;  any  obstruction  to  the 
hepatic  duct,  without  the  liver  being  involved  in  the 
disease,  may  give  rise  to  the  skin  affection,  as  Dr. 
Moxon's  case  shows.*  I  think  it  will  prove  doubtful  if 
the  xanthelasma  associated  with  jaundice  be  more  com- 
mon amongst  men  than  woman.  Mr.  Hutchinson 
found  that  xanthelasma  from  all  causes  was  twice  as 
common  in  women  as  in  men.f  Few,  however,  of  his 
cases  were  jaundiced.  In  my  own  experience,  I  have 
met  with  six  cases  of  jaundice  associated  with  xanthe- 
lasma.    Four  of  these  were  men  ;  two  women. 

As  to  the  age  of  the  patient,  it  is  generally  thought 
that  xanthelasma  does  not  attack  young  persons.  I 
have,  however,  met  with  a  case  of  xanthelasma  and 
jaundice  in  a  girl  aged  18  years :  Kaposi,  a  doubtful 
case  indeed  without  jaundice,  in  a  young  man,  aged  24, 
who  had  patches  of  xanthelasma  the  size  of  wheat  corns 
at  the  root  of  the  penis,  J  and  another  doubtful  case 
spoken  of  by  Dr.  Pye-Smith  in  a  boy  aged  18  asso- 
ciated with  jaundice. §  The  greatest  age  at  which 
xanthelasma  from  jaundice  seems  to  have  been  ob- 
served is  Dr.  Pye-Smith's  case  in  which  the  xanthe- 
lasma appeared  at  the  age  of  57.II  It  is  hard,  however, 
among  the  poor  to  be  sure  of  the  age  at  which  xanthe- 
lasma appears.  Often  it  happens  that  they  are  quite 
ignorant  of  the  existence  of  the  patches  until  they  are 
pointed  out  to  them  ;  and  this  no  matter  what  the 
cause  of  the  disorder. 

Xanthelasma  was  divided  by  Addison  and  Gull  into 

*  Moxon,   Transactions  of  the  Pathological  Society  of  Lond.  1873,  Vol.   xxiv 
p.  129. 

f  Hutchinson,  op.  cit.  p.  175. 

X  Kaposi,  op.  cit.  p.  256,  note. 

§  Pye-Smith,  Gtiy's  Hosp.  Reports,  1877,  P-  ^o^' 

jj  Pye-Smith,  Transactions  of  the  Path.  Soc.  of  Lond.  1873,  Vol.  xxiv.  p.  250. 


320  Varieties  of  Xanthelasma. 

vitiligoidea  plana,  and  tuberosa.  The  flat  variety  is 
chiefly  met  with  on  the  eyehds,  commonly  on  the  inner 
half,  and  arranged  with  symmetry  on  each  side.  It  is 
seen  also  in  the  face  and  cheeks,  on  the  conjunctiva, 
and  the  mucous  membranes  of  the  mouth  and  air-tubes. 
It  may  be  seen  also  on  the  prepuce  and  glans  penis  * 
and  even  under  the  nails.  They  vary  from  a  pin's 
point  to  a  florin  in  size ;  Kaposi  says  he  has  seen  some 
as  large  as  a  thaler. f  They  are  of  a  pale  yellow  white 
colour,  like  a  dead  leaf,  slightly  raised  above  the  sur- 
rounding skin  or  mucous  membrane,  soft,  and  irregular, 
but  tending  to  the  form  of  a  circle.  They  cause  no  pain 
or  inconvenience,  for  the  patients  are  often  not  aware 
of  their  presence. 

A  variety  of  the  plane  is  the  linear  form  of  xanthe- 
lasma, best  seen  in  the  palm  as  white  lines  following 
accurately  the  flexures  caused  by  the  bending  of  the 
hand  and  fingers.  It  is  also  seen  in  the  soles  along  the 
flexures  of  the  toes. 

The  favourite  seats  of  the  tuberose  variety  of  xanthe- 
lasma are  the  ears,  neck,  and  trunk ;  the  back  of  the 
elbows,  and  hands,  knuckles  of  the  fingers  ;  in  the 
ham,  knees,  and  on  the  feet.  It  is  seen  small  as  a 
millet  seed,  or  of  the  size  of  a  horse  bean,  the  patches 
may  seem  much  larger  if  individual  tubercles  become 
confluent.  The  skin  over  the  tubercles  is  smooth, 
sometimes  shining,  and  moves  with  them.  In  some 
cases  of  tuberose  xanthelasma  of  the  knuckles,  the 
spots  have  been  adherent  to  the  extensor  tendon  under- 
neath. 

The  tuberose  form,  unlike  the  plane,  shows  a  disposi- 
tion to  cause  annoyance  to  the  patient.  In  some 
cases,  tools  could  no  longer  be  handled,  walking  and 
sitting  only  be  accomplished  with  trouble.      There  is 

•  Hillairet,  Bulletin  dc  V Academic  dc  Med.  1878,  42me  annee,  p.  1172. 
f  That  is,  bigger  than  our  half-crown.     Kaposi,  op.  cit.  p.  253. 


J'i^ 


\ 


4 


Pathology  of  Xanthelasma.  321 

sometimes  a  feeling  of  burning  and  itching,  though  it 
is  doubtful  how  much  of  this  may  be  due  to  the  pre- 
sence of  the  jaundice.  The  tubercle,  if  cut  across, 
bleeds  profusely. 

All  forms  of  xanthelasma  show  a  tendency  to  symme- 
try, whether  appearing  on  the  limbs  or  on  the  mucous 
membrane.  Thus  both  eyelids  are  usually  affected, 
both  hands  and  elbows.  In  a  case  of  my  own,  the 
mucous  membrane  on  both  sides  of  the  tongue  was 
seized  on  by  xanthelasma  in  a  markedly  symmetrical 
manner.  (See  No.  I.  and  No.  II,  of  the  chromo-litho- 
graphs,  and  the  case  of  Charles  Kingsley,  at  p.  327,  of 
this  work.) 

Even  when  jaundice  is  the  cause  of  xanthelasma,  the 
patches  would  seem  to  first  appear  in  the  neighbour- 
hood of  the  eyelids,  and  in  many  cases  to  spread  no 
farther.  In  much  rarer  cases  the  xanthelasma  appears  all 
over  the  body,  and  is  then  called  xanthelasma  multiplex. 

As  to  the  nature  of  xanthelasma :  Hebra  seems  at 
first  to  have  believed  that  xanthelasma  was  due  to  some 
sebaceous  obstruction,  like  milium  or  comedo.*  Against 
this  view,  it  may  be  urged  that  when  a  spot  of  xanthe- 
lasma is  cut  across,  nothing  but  a  bloody  fluid  can  be 
pressed  out,  no  white  accumulation  can  be  removed, 
and  the  yellow  spot  cannot  be  got  rid  of  by  pressure. 
This  view  of  xanthelasma  has,  indeed,  I  think  been 
given  up  by  its  author,  and  the  view  expressed  by  Dr. 
Pavy  now  prevails.  He  was  the  first  to  examine  a  no- 
dule of  xanthelasma  with  the  microscope,  and  found  it 
to  be  formed  of  a  very  dense  fibrous  tissue,  pervaded 
with  fat  granules. t 

Waldeyer  was,  however,  the  first  to  give  a  full  and 
accurate  account  of  the  xanthelasma  palpebrarum.     He 

*  Hebra,  Atlas  d.  Hautkrankheiten,  Lief.  7,  and  Diseases  of  the  Skin,  Trans,  by 
Hilton  Fagge,  New  Sydenham  Soc.  1866,  Vol.  i.  p.  127. 
f  Pavy,  Guy^s  Hasp.  Reports,  1866,  p.  282. 

Y 


322  Waldeyer's  Views  on  Xanthelasma. 

found  that  the  yellow  colour  was  due  in  but  a  very  small 
degree  to  the  increase  of  the  stellate  pigment  cells  which 
may  naturally  be  found  in  the  eyelids.  These  cells  were 
met  with  in  numbers  only  slightly  greater  than  usual. 
They  were  found  near  the  epidermis  and  especially 
about  the  hair  follicles,  vessels,  and  nerves,  yet  never 
so  thickly  set  together  that  the  yellow  colour  of  the 
xanthelasma  patch  could  be  caused  by  it.  The  chief 
change  in  xanthelasma  is  a  great  multiplication  of  the 
connective  tissue  corpuscles  in  those  places  where  natu- 
rally in  the  eyelid  they  are  more  numerously  grouped 
together :  therefore  around  the  hair  follicles,  glands, 
vessels,  and  nerves.  There  follows  upon  this  a  fatty 
degeneration  of  these  new-formed  cells.  So  both  these 
processes  together  explain  the  physical  characters  of 
xanthelasma,  the  formation  of  yellow  raised  patches. 
Thus  Hebra  is  quite  wrong,  as  the  whole  process  takes 
place  in  the  connective  tissue  of  the  eyelids,  and  not  in 
the  glands.  It  is  thus  an  interstitial  and  not  a  paren- 
chymatous process.  But  although  xanthelasma  has 
many  points  in  common  with  dermatitis,  new  forma- 
tions in  the  skin,  and  syphilis,  yet  notwithstanding  it 
has  something  peculiar  in  itself.  The  fat,  for  example, 
in.  the  new-formed  cells  is  not  so  granular  as  in  or- 
dinary fatty  degeneration,  large  drops  are  readily 
formed  ;  without,  however,  forming  ordinary  fat  cells. 
The  deposition  of  fat  likewise  seems  to  have  no  harmful 
effect  upon  the  cells  themselves  ;  as  after  the  fat  is 
taken  away  by  reagents,  the  cell  is  always  found  with 
nucleus  and  protoplasm,  even  after  the  xanthelasma 
has  lasted  many  years,  and  thus  Waldeyer  has  never 
met  with  softening,  a  milky  detritus,  masses  of  choles- 
tearin,  or  calcification,  accidents  commonly  seen  after 
fatty  degeneration.  Xanthelasma  never  seems  to  under- 
go a  retrogressive  metamorphosis,  and  this  is  one  of  its 
most  interesting  peculiarities.* 

*  Waldeyer,  Arch.  f.  path.  Anat.  iSji,  Bd.  lii.  p.  318. 


Vir chow's  Views  on  Xanthelasma.  323 

Leber  has  confirmed  these  observations  in  a  case  of 
xanthelasma  multiplex  reported  by  Virchow.  In  the 
smaller  tubercles  of  xanthelasma,  however,  no  fatty 
infiltration  of  the  cells  was  to  be  seen  ;  only  a  few  cells 
contained  a  few  yellow  to  yellow-brown  pigment  gran- 
ules.* Still  it  would  seem  certain  that  the  colour  of 
xanthelasma  is  due  to  fat  and  not  to  pigment  ;  and 
this  is  the  more  remarkable  since  jaundice  is  attended 
by  a  deposit  of  pigment  in  the  skin.  Waldeyer's  account 
of  xanthelasma  palpebrarum  may,  I  think,  be  safely  ap- 
plied to  the  xanthelasma  of  the  rest  of  the  body.  I 
have  examined  patches  from  the  tongue  and  the  scro- 
tum, and  found  very  nearly  the  same  appearances  as  he 
has.  In  the  scrotum  the  cuticle  was  not  thickened  over 
the  patches  ;  collections  of  oil  globules  in  long  streaks 
were  seen  in  the  deeper  layers  of  the  subcutaneous  con- 
nective tissue.  In  some  cases  there  was,  as  Waldeyer 
has  described,  an  accumulation  of  oil  globules  around 
the  hair  follicles,  vessels,  and  other  structures  passing 
through  the  skin  ;  but  this  was  not  universally  true. 
The  papillae  of  the  skin  seemed  unaffected ;  the  collec- 
tion of  oil  drops,  though  somewhat  bent  towards  the 
papilla  as  it  passed  under  it,  did  not  enter  it.  When 
examined  with  a  high  power,  the  collection  of  fat  drops 
showed  many  cells,  varying  much  in  size.  The  very 
smallest  were  not  so  large  as  a  red  blood  corpuscle, 
and  were  round,  oval,  rhomboidal,  and  spindle  shaped. 
These  small  cells  were  free  from  granular  contents ; 
showing  one  or  even  two  nuclei.  The  cells  larger  than 
these  were  slightly  granular.  Then  there  were  cells 
four  or  six  times  the  size  of  the  smallest ;  round  or  oval  in 
shape ;  filled  with  fat,  and  therefore  no  nucleus  to  be  seen. 
The  fat  was  not  in  many  drops  but  in  one  large  drop, 
distending  the  cell. 

Some  of  these  large  fat-containing  cells  had  a  sinuous 

*  Leber,  reported  by  Virchow,  ibid.  p.  506. 

Y2 


324  Xanthelasma  not  a  fatty  degeneration 

appearance;  apparently  brought  about  by  the  pressure  of 
the  fibres.  The  patches  of  the  tongue  showed  appear- 
ances, in  all  important  respects  like  those  of  the  scrotum. 
It  is  thus  evident  that  the  xanthelasma  of  the  mucous 
membranes  and  the  xanthelasma  of  the  skin  are  alike  in 
their  nature.  The  same,  however,  cannot  be  predicated 
of  the  yellow  patches  seen  under  serous  membranes  in 
cases  of  multiple  xanthelasma.  I  have  examined  these 
spots,  which  to  the  naked  eye  closely  resemble  those  of 
xanthelasma,  and  find  that  the  appearance  is  caused  by 
a  spindle-shaped  cavity  in  the  connective  tissue  under 
the  peritonseum,  filled  with  ordinary  adipose  tissue. 
These  patches,  therefore,  differ  altogether  in  nature 
from  xanthelasma,  and  seem  to  be  a  mere  local  accu- 
mulation of  fat  under  the  peritonseum. 

There  is,  undoubtedly,  a  superficial  resemblance  in 
the  process  seen  in  xanthelasma  to  that  of  atheroma  in 
the  arteries.  The  great  difference  between  them  lies, 
as  Virchow  has  pointed  out,  in  the  absence  of  any  true 
fatty  degeneration.*  Both  in  xanthelasma  and  athe- 
roma there  is  a  chronic  process  of  cell  growth,  followed 
by  a  fatty  infiltration  of  the  cells  ;  but  in  xanthelasma 
there  is  no  fatty  degeneration  ;  the  cells  do  not,  as  in 
atheroma,  break  up  and  form  a  fatty  detritus,  a  change 
followed  in  time  by  the  formation  of  cholestearin,  by 
calcification,  and  ulceration.  Xanthelasma  may  last 
for  years,  and  yet  the  cells,  although  filled  with  fat,  are 
perfectly  retained,  and  no  retrogressive  changes  are 
met  with.  Mr.  Howse,  however,  has  seen,  in  a  case  of 
Dr.  Hilton  Fagge's,  appearances  of  further  degenera- 
tive changes,  the  middle  part  of  the  patch,  as  in  athe- 
roma, being  converted  into  lumps  of  calcareous  matter 
and  crystalline  bodies. f    From  these  appearances  it  was 

*  Virchow,  op.  cit.  p.  507.     Cf.  Waldeyer,  ibid.  p.  322. 

f  Howse,  reported  by  Hilton  Fagge,  Trans,  of  the  Path.  Soc.  of  Land.  1873, 
Vol.  xxiv.  p.  244. 


but  a  fatty  infiltration.  325 

judged  that  xanthelasma  and  atheroma  were  identical 
in  nature.  This  opinion  can,  however,  hardly  be  ac- 
cepted, as  it  is  opposed  to  the  observation  of  all  other 
histologists,  until  many  other  cases  of  xanthelasma  of 
the  same  kind  have  been  examined,  and  like  appear- 
ances of  fatty  degeneration  found.  The  spontaneous 
disappearance  of  xanthelasma  without  scarring  is  also 
against  the  idea  of  a  fatty  degeneration. 

The  greater  number  of  observers,  beginning  with  Dr. 
Pavy,  maintain  that  there  is  great  over-growth  of  fibrous 
tissue  in  xanthelasma,  and  on  this  ground  Virchow  has 
proposed  to  call  it  Fibroma  lipomatodes  or  molhiscum 
lipomatodes.  In  my  own  case  the  overgrowth  of  the 
connective  tissue  was  not  so  very  apparent :  neither 
does  it  seem  to  have  greatly  struck  Waldeyer.  A  very 
great  development  of  the  fibrous  element  of  the  con- 
nective tissue  would  seem  incompatible  with  great  cell 
growth  ;  and  xanthelasma,  as  felt  by  the  finger  during 
life,  does  not  give  the  impression  of  hardness.  It  is 
probable  that  one  of  the  distinctions  between  the  flat 
and  tubercular  varieties  of  xanthelasma  lies  in  the 
amount  of  connective  tissue  present. 

Another  point  in  which  observers  differ  is  the  thick- 
ening of  the  cuticle  over  the  patch.  Leber*  and  Dr.  Frank 
Smithf  found  an  increase  in  thickness  of  the  epidermis; 
Dr.  Murchison  found  no  change  in  the  epidermis,  J  an 
appearance  also  met  with  in  a  case  which  I  had  the 
opportunity  of  examining. §  Mr.  Howse,  indeed,  in 
some  specimens  of  xanthelasma  taken  from  the  trachea 
found  no  epithelium  over  the  patches,  an  appearance 
doubtless  due  to  changes  after  death,  yet  some  evidence 
that  no  increase  of  epithelium  existed  during  life.|| 

*  Leber,  loc.  cit. 

f  Frank  Smith,  Journal  of  Cutaneous  Medicine,  iS5g,  Vol.  iii.  p.  244. 

X  Murchison,  Trans,  of  the  Path.  Soc.  of  Lond.  iS6g,  Vol.  xx.  p.  191. 

§  See  p.  333  of  this  work. 

II  Howse,  loc.  cit. 


326  Chambard's  Observations. 

Within  the  last  twelvemonth  Chambard  has  published 
a  further  account  of  the  histology  of  xanthelasma. 
His  description  of  the  tubercular  and  plain  varieties  of 
xanthelasma  differs  but  little  from  that  given  by  former 
histologists  ;  but  some  details  are  added  as  to  the  state 
in  the  tubercular  variety  of  the  vessels  and  nerves, 
which,  he  says,  have  not  yet  been  described.  The 
arteries  show  an  endo-arteriitis,  which  may  block  up 
the  bore  of  the  vessel,  and  the  peri-arteriitis,  with  an 
active  formation  of  connective  tissue,  is  especially  well- 
marked.  The  nerve-tubes  are  soldered  together,  and 
the  tissue  much  thickened.  Chambard  thinks  that  this 
implication  of  the  nerves  in  the  xanthelasma  tuber- 
osum explains  the  pain  and  itching  which  are  felt  in 
this  variety,  but  not  in  the  plane.* 

It  would  seem  that  the  diagnosis  of  xanthelasma 
ought  always  to  be  easy.  The  only  other  skin  disease 
with  which  it  may  be  confounded  is  milium  or  comedo, 
and  from  this,  xanthelasma  may  be  distinguished  by  the 
ready  enucleation  of  the  contents  of  the  sebaceous  cyst 
when  the  skin  over  it  is  divided,  while  nothing  can  be 
squeezed  out  of  the  patch  of  xanthelasma  but  blood  and 
a  milky  fluid.  I  do  not  feel  at  all  confident  that  some  of 
the  appearances  figured  by  Mr.  Hutchinson  as  xanthe- 
lasma are  not  milium.  One  of  the  patches  has  a  seba- 
ceous plug  in  its  centre. t  It  is  plain  therefore  that  the 
diagnosis  is  not  always  one  which  can  readily  be  made. 
As  to  the  possible  disappearance  of  xanthelasma 
multiplex,  I  have  seen  a  large  crop  of  xanthelasma 
tuberosum,  planum,  and  lineare  completely  disappear 
in  three  years,  and  leave  no  trace  or  scar  behind,  so 
that  it  could  not  be  thought  that  the  skin  had  been  the 
seat  of  such  extensive  changes,  and   this  without  any 

*  Chambard,  Bulletin  dc  I' Academic  de  Medecine,  1878,  42me  annee,  p.  1173. 

f  Hutchinson,  Med.  Chir.  Trans.  187J,  Vol.  liv.  plate  iii.  fig.  2.  Kaposi  shares 
the  doubt  expressed  in  the  text.  (Hebra's  Hautkrankheiten,  2te  Auflage,  in 
Virchow's  Handb.  d.  spec.  Path.  u.  Ther.  Stuttgart,  1S76,  p.  252  note.) 


Treatment  of  Xanthelasma.  327 

change  in  the  jaundice.  As  the  eyeHds  are  the  first  to 
suffer,  so  they  appear  to  be  the  last  to  recover,  as  in 
this  case  the  man  still  showed  well-marked  patches 
(though  much  smaller)  near  the  inner  angle  of  the 
eyelids.*  In  one  of  Dr.  Hilton  Fagge's  cases  the 
patient  told  him  that  some  of  the  patches  had  dis- 
appeared, apparently  in  a  fortnight  ;t  but  on  comparing 
her  state  with  notes  taken  before,  it  rather  appeared 
that  the  disease  was  aggravated.  In  Dr.  Frank  Smith's 
case  the  patches  certainly  grew  less.  J 

As  to  the  treatment  of  xanthelasma,  no  drug  is  at 
present  known  to  have  any  influence  in  removing  the 
spots.  Excision  by  the  knife  is  certainly  to  be  avoided, 
especially  in  the  neighbourhood  of  the  eye,  where  the 
healing  of  the  wound  may  lead  to  eversion  of  the  eyelid. 


Hydatids  of  the  Liver,  Omentum,  and  Recto-vesical  Pouch  :    yaundice  : 
Xanthelasma  of  the  Tongue,  Eyelids,  and  Skin.^ 

Charles  Kingsley,  ag"ed  35,  a  cattle-dealer,  married,  came  to  me 
in  September,  1873,  at  S.  Bartholomew's  Hospital,  as  an  out-patient. 
He  was  then  deeply  jaundiced,  and  had  been  so  for  nine  months. 
He  said  he  was  not  a  drunkard,  and  had  not  had  syphilis.  He 
had  never  felt  any  pain  in  his  right  side.  The  urine  gave  a  very 
marked  reaction  with  Gmelin's  test.  The  left  lobe  of  the  liver  was 
much  enlarged,  even  down  to  the  umbilicus.  •  The  surface  smooth, 
but  the  edge  sharp.  There  was  well-marked  xanthelasma  palpe- 
brarum, and  there  were  also  two  yellow  spots  the  size  of  pin-heads 
on  the  palpebral  conjunctiva  of  right  eye,  and  one  like  these  on 
caruncle  of  left.  There  were  spots  of  xanthelasma  on  palms  of  the 
hands  and  left  elbow,  on  the  right  ear  and  left  side  of  the  nose. 
The  tongue  was  purplish  ;  along  its  sides  were  patches,  yellowish 
white,  oblong,  quite  soft,  but  slightly  raised  :  also  a  yellow  spot 
on  the  middle  line  of  the  roof  of  the  mouth,  and  another  near  the 
lingual  vein.     (See  No.  I.  of  the  chromo-lithographs.) 

*  See  p.  337  of  this  work  for  the  case  at  length. 

f  Hilton  Fagge,  Trans,  of  Path.  Soc.  of  Land.  1868,  Vol.  xix.  p.  438. 
I  W.  Frank  Smith,  ibid.  1877,  Vol.  xxviii.  p.  236. 

§  This  case  has  been  published  in  the  Trans,  of  the  Path.  Society  of  London,  1S74, 
Vol.  XXV.  p.  155,  and  in  St.  Bartholomew's  Hospital  Reports,  1874,  Vol.  x.  p.  244. 


328  Cases  of  Xanthelasma. 

This  patient  was  admitted  into  Matthew's  Ward  on  November 
i8,  1873. 

Dr.  Herbert  Taylor,  who  was  then  house-physician,  has  fur- 
nished me  with  the  following-  clinical  notes. 

On  admission,  the  patient  said  he  was  quite  well  up  to  last 
October  twelve  months.  He  was  never  jaundiced  before  that 
time.  He  then  began  to  feel  weak  and  depressed,  and  about  the 
same  time  he  was  told  he  was  becoming  yellow.  During-  these 
twelve  months  he  had  had  remissions  of  the  jaundice,  remaining 
clear-coloured  for  three  or  four  days  together.  Such  remissions 
have  occurred  about  twice  in  a  month.  He  has  not  suffered  any 
pains  whatever  till  the  last  six  weeks;  then,  about  ten  minutes 
after  taking  any  meal,  he  is  seized  with  pain  as  though  his  bowels 
were  being  tied  in  a  knot,  at  the  same  time  his  belly  swells,  and  he 
suffers  from  wind.  The  pain  lasts  from  half  an  hour  to  three- 
quarters.  For  the  last  six  weeks  he  has  had  difficulty  in  passing- 
his  stools,  and  with  this,  occasionally  a  little  blood  with  straining". 
The  stools  are  always  clay-coloured  and  hard,  even  in  the  remis- 
sions of  the  jaundice.  Micturition  during  the  last  week  has  been 
very  painful ;  a  small  stream,  occasionally  stopping-.  Before  this 
the  urine  was  abundant,  always  dark,  and  staining  the  linen,  even 
in  the  remissions  of  jaundice. 

He  has  lost  flesh  considerably  during  the  last  year;  he  thinks 
about  two  stone.  He  has  not  been  a  spirit-drinker,  but  has  taken 
much  beer. 

His  legs  began  to  swell  about  five  weeks  ago ;  they  are  now 
much  less  swollen.  His  skin  does  not  itch  much,  chiefly  the  head 
itches. 

Has  always  been  .  a  healthy  man,  although  exposed  to  all 
weathers. 

He  is  married,  and  has  six  children.  He  has  never  had  gonor- 
rhoea. 

November  19.  A  thin,  care-worn  man,  blue  eyes,  sandy-red 
hair  ;  lying  most  comfortably  on  his  back.  The  whole  body 
coloured  of  an  uniform  dark  yellow  tint.  Conjunctivae  yellow, 
pupils  contracted.  He  does  not  see  nor  has  he  ever  seen  yellow. 
On  certain  parts  of  his  body  are  patches,  irregular  in  shape,  as- 
suming more  the  form  of  the  parallelogram  than  the  circle,  of  a 
pale  yellow- white  colour,  paler  than  the  surrounding  integument, 
denser  to  the  touch,  but  moving  freely  with  the  skin  over  the  subjacent 
textures;  smooth  surface,  not  raised;  in  size  from  I  line  by  2  lines 
to  half  an  inch  by  half  an  inch.  The  parts  thus  aflFected  are  :  the 
inner  canthus  of  each  eye  and  adjacent  skin,  one  in  palpebral  con- 


Cases  of  Xanthelasma.  329 

junctiva  of  left  lower  eyelid,  one  larger  over  right  temporal  region 
(zygoma),  on  the  helix  of  the  right  ear,  on  the  nape  of  the  neck; 
many  small  patches  on  ball  of  thumbs,  one  on  ball  of  left  little 
finger,  ulnar  extremity,  around  the  root  of  the  penis  at  junction  of 
skin  of  scrotum  with  abdomen,  and  in  the  perinaeum ;  none  below 
this  point ;  in  the  flexures  of  the  fingers  of  both  hands,  but  not  in 
the  toes  ;  stains  of  old  purpura  on  lower  arms  and  the  legs.  Scat- 
tered over  the  abdomen  and  back,  scantily,  are  pustules,  broken 
down  by  scratching.  In  the  mucous  membrane  of  the  lower  lips 
are  two  small  patches,  similar  in  appearance  to  the  patches  seen 
on  the  skin.  Along  each  side  of  the  tongue,  reaching  from  behind 
forwards  to  the  tip,  not  appearing  on  the  upper  surface,  are  masses 
of  tissue  of  similar  appearance,  somewhat  symmetrical. 

Pulse  72,  regular;  radial  artery  atheromatous;  temperature 
97-8°  F.  Chest  well  formed,  movements  equal  on  both  sides. 
Heart's  apex  beats  in  the  third  left  intercostal  space,  half  an  inch 
above  and  to  inner  side  of  left  nipple.  Sounds  normal.  Reson- 
ance good  from  above  downwards  to  lower  border  of  third  rib  or 
third  interspace  on  right  side ;  from  that  level  down  to  two  fingers' 
breadth  below  margin  of  cartilages  is  dulness.  On  the  left  side 
resonance  downwards  to  level  of  heart's  apex;  from  thence  dul- 
ness downwards  beyond  the  cartilages  to  a  level  of  one  and  a  half 
inches  above  umbilicus.  Posteriorly  the  liver  dulness  encroaches 
on  the  chest ;  good  breathing  sounds  over  area  of  resonance. 

Abdomen  :  distended,  resonant  below  the  limits  of  dulness  just 
described  down  to  the  pubes  and  to  each  iliac  fossa,  except  in  left 
iliac  fossa,  where  is  an  area  of  semi-dulness,  oval  in  outline,  corre- 
sponding to  an  area  of  resistance  to  the  touch,  which  is  not  so  in 
right  iliac  fossa.  Splenic  dulness  nil.  The  dulness  in  the  epigas- 
trium and  hypochondria  above  described  corresponds  to  a  tumour 
which  is  felt  in  that  situation,  the  margin  of  which  reaches  from 
the  lower  border  of  the  ninth  costal  cartilage  on  the  right  side, 
passes  horizontally  inwards  to  middle  line,  and  then  passes  verti- 
cally downwards  to  an  inch  and  a  lialf  above  umbilicus,  and  again 
extends  horizontally  to  cartilages  on  left  side,  where  it  is  lost. 
Surface  smooth  and  firm.  The  edge  on  the  right  side  is  thick,  on 
the  left  quite  sharp  and  firm.  There  is  also  a  small  umbilical 
hernia,  which  he  has  noticed  only  for  a  fortnight. 

There  is  a  considerable  oedema  of  the  feet  and  ankles. 

November  20.  Slept  fairly,  tongue  furred,  white,  moist;  very 
thirsty,  good  appetite  ;  no  nausea.  Pulse  yG;  temperature  97°  F. 
Urine  deeply  coloured  by  bile,  sp.  gr.  1012,  acid,  a  slight  cloud  of 
albumen  ;  griping  abdominal  pain. 


330  Cases  of  Xanthelasma, 

2 1st.  Slept  badly;  no  pain  ;  tongue  clean,  moist.  Bowels  open 
twice.     Pulse  76. 

22nd,  Slept  well;  bowels  acted  with  pain.  Pulse  So;  tempera- 
ture 98°. 

24th.   ■  Slight  pain  in  belly.     Pulse  80 ;  temperature  966°. 

December  i.  He  has  been  sitting  up  during  the  week ;  he  feels 
easier ;  there  was  more  difficulty  yesterday  in  passing  his  water. 
A  restless  night.  Tongue  clean,  moist,  red;  oedema  of  legs  and 
feet  has  increased.     Pulse  80,  full  and  regular. 

2nd.  Slept  well;  no  pain.  Slight  tenderness  in  right  hypo- 
chondrium  ;  vomited  this  morning  after  breakfast;  tea  makes  him 
sick.     Pulse  80. 

4th  (i0'30  A.M.).  Slept  very  badly.  This  morning  there  is  slight 
wandering;  very  severe  pain  over  lower  abdomen,  right  groin,  end 
of  penis,  and  down  right  thigh.  He  lies  coiled  upon  his  left  side. 
Micturition  painful ;  a  small  stream,  but  it  does  not  stop  in  pass- 
ing; urine,  no  albumen,  bile-stained.  Belly  very  tender;  tongue 
parched,  furred;  thirsty,  drowsy ;  bowels  open.  Pulse  130,  re- 
spiration 30,  temperature  106°.  At  2  p.m. — Pulse  135,  temperature 
105*6°.  Lies  on  his  right  side;  knees  drawn  up;  has  passed  water 
since  the  morning. 

10*30  P.M.     He  is  quite  unconscious.     Temperature  102*4°  F. 

5th  (2*30  P.M.).  Quite  unconscious.  Pulse  144;  temperature 
105*4°. 

He  died  at  six  in  the  evening. 

Examination  eighteen  hours  after  death.  Body  of  a  universal  deep 
yellow,  and  wasted;  shins  and  feet  oedematous.  Rigor  mortis 
well  marked ;  the  veins  in  skin  covering  iliac  fossae,  Scarpa's 
triangle,  and  front  of  chest  already  shown  by  purple  lines.  No 
other  signs  of  decomposition. 

Well  marked  xanthelasmic  patches  on  eyelids,  right  ear  (one  of 
these  is  covered  by  a  scab  of  dried  blood),  scrotum,  bend  of 
elbows,  flexures  of  hands,  neck,  and  shoulders.  Along  the  furrows 
of  the  hands  they  are  seen  as  long,  narrow  lines.  Over  belly  are 
three  or  four  spots  covered  with  dried  blood.  No  other  ecchy- 
moses  on  skin. 

Calvaria  is  natural ;  dura  mater  of  a  deep  yellow;  longitudinal 
sinus  empty.  Membranes  and  arteries  of  brain  natural ;  so  also 
ventricles,  central  ganglia,  and  rest  of  brain. 

The  inside  of  body  quite  warm.  A  layer  of  fat  under  skin. 
The  cartilages  are  white,  the  ribs  green.  No  fluid  in  either 
pleura.     A  greenish  fluid  in  pericardium.     The  heart's  apex  is  on 


Cases  of  Xanthelasma.  331 

the  level  of  the  lower  border  of  third  rib,  or  upper  part  of  third 
interspace.     All  the  contents  of  the  chest  are  pushed  upwards. 

The  heart  natural ;  aortic  and  mitral  valves  somewhat  athero- 
matous: lungs  natural. 

Tongue :  there  is  a  yellow  raised  spot,  the  size  of  a  mustard- 
seed,  on  the  dorsum.  Along  each  side  there  are  three  or  four 
irregular  yellowish-white  spots.  They  are  sharply  defined, 
varying  in  size  from  split  peas  to  a  sixpence.  Two  of  those 
nearest  the  tip  show  a  loss  of  substance,  and  they  are  also  covered 
with  a  crust  of  dried  blood.  The  under  surface  of  the  tongue 
shows  two  or  three  yellowish  spots  the  size  of  mustard-seeds. 

The  soft  palate,  pharynx,  and  lower  parts  of  the  oesophagus  are 
free  from  yellow  spots.  Just  where  the  oesophagus  begins  is  a 
cluster  of  numerous  yellow  spots  for  about  an  inch.  There  is  a 
yellow  spot  the  size  of  a  mustard-seed  at  the  forepart  of  the 
larynx,  where  the  two  vocal  chords  meet.  The  ridge  of  the  bifur- 
cation of  the  trachea  shows  a  yellow  spot.  The  rest  of  the  larynx, 
trachea,  and  bronchial  tubes,  which  were  carefully  examined,  show 
no  yellow  patches  which  could  be  confounded  with  xanthelasma. 

The  peritonaeum,  covering  the  recti  on  both  sides,  is  speckled 
yellow  with  small  patches.  They  are  tolerably  numerous,  and  in 
clusters.  Other  parts  of  the  peritonaeum  do  not  show  this  appear- 
ance. 

The  great  omentum  is  adherent  to  the  distended  bladder.  To 
the  left  there  is  a  swelling  of  the  size  and  shape  of  a  grown-up 
man's  kidney.  It  is  within  the  omentum,  but  is  adherent  also  to 
the  sigmoid  flexure  of  the  colon.  Opened  it  is  found  to  contain  an 
hydatid  cyst,  which  encloses  very  many  small  daughter  cysts, 
varying  in  size  from  a  mustard-seed  to  a  large  marble. 

The  stomach  and  small  intestines  are  natural.  There  are  no 
yellow  patches  either  on  their  mucous  or  peritonseal  surface.  The 
contents  of  the  small  intestines  quite  colourless.  The  contents 
of  the  large  intestine  are  also  white  and  solid ;  but  in  many  places 
they  have  a  coating  of  clotted  blood.  The  mucous  membrane 
of  the  large  intestine  from  the  caecum  to  the  sigmoid  flexure  shows 
innumerable  ecchymoses,  very  fine,  and  surrounded  with  fine 
injection.  The  rectum  natural.  Contents  colourless,  solid,  un- 
stained by  blood. 

The  bladder  is  dilated;  it  holds  about  a  pint  of  urine,  almost 
black.  This  urine  gives  a  decided  cloud  on  applying  heat  and 
nitric  acid.  There  is  a  well-marked  green  colour  with  Gmelin's 
test.     It  contains  urea;   something  over  '6 per  cent. 

Filling  the  pelvis  between  the  bladder  and  the  rectum,  and  mak- 


332  Cases  of  Xanthelasma. 

ing  the  removal  of  these  organs  difficult,  is  a  tumour  the  size  of  a 
child's  head.  It  proves  to  be  another  hydatid  cyst,  but  contains  no 
daughter  cysts. 

On  dissecting  the  porta  of  the  liver,  the  portal  vein  is  found  to 
contain  fluid  blood.  Swollen  lympathic  glands  surround  the 
bile-ducts.  The  common  bile-duct  is  quite  free  from  colour ;  so 
also  the  cystic.  The  gall  bladder  contains  about  an  ounce  of  a 
slightly  viscid,  colourless  fluid.  This  fluid  is  rendered  cloudy 
by  acetic  and  nitric  acids;  it  is  rendered  more  viscid  by  caustic 
soda,  Gmelin's  and  Pettenkofer's  tests  repeatedly  applied  give 
no  trace  of  colour.  Half  an  inch  above  the  opening  of  the  cystic 
duct,  the  canal  of  the  hepatic  duct  is  completely  obstructed  by  a 
swelling  from  within  the  liver.  Just  before  the  obstruction 
becomes  complete,  the  duct  contains  a  semi  solid  mass  of  green 
pigment.  The  duct  then  passes  over  the  wall  of  the  tumour, 
and  cannot  be  traced  for  about  an  inch.  Dissecting  beyond  the 
tumour,  the  hepatic  duct,  dilated  to  the  size  of  a  man's  middle 
finger,  and  containing  a  colourless  fluid,  is  open.  It  receives 
many  large  openings  of  dilated  bile-ducts,  which  also  contain  a 
colourless  fluid.  Following  by  dissection  these  ducts,  it  is  found 
that  those  in  the  left  lobe  are  more  dilated  than  in  the  right. 
From  those  ducts  in  which  the  surface  has  been  scraped  imme- 
diately after  their  being  opened,  the  scrapings  under  the  micro- 
cope  show  abundance  of  well-formed  cylindrical  epithelium.  No 
cylindrical  epithelium  can  be  seen  in  the  scrapings  from  those 
ducts  which  have  been  washed  with  water  or  touched  with  a 
sponge. 

Although  the  large  ducts  contain  a  colourless  fluid,  and  are 
quite  white,  yet  this  is  not  the  case  with  the  smaller.  They  are 
stained  a  pale  yellow,  and  on  pressing  the  liver  a  yellow  fluid  can 
be  made  to  come  out  of  them.  No  yellow  spots  can  be  noticed  in 
any  of  those  opened. 

Lying  in  the  body,  the  left  lobe  of  the  liver  passes  for  nearly 
two  inches  below  the  level  of  the  right.  Taken  out,  the  liver 
weighs  140  oz.  Its  colour  is  a  deep  olive  green,  mottled  with 
yellow  ;  surface  smooth.  On  the  upper  surface  of  right  lobe,  near 
suspensory  ligament,  are  seen  two  irregular  spots,  about  the  size 
of  penny-pieces,  of  a  yellowish  colour;  they  exactly  resemble  the 
spots  which  may  be  made  by  pressure  on  a  natural  liver  after 
death.  A  similar  spot  exists  farther  back  on  the  upper  surface. 
A  cyst  projects  at  the  back  of  the  liver,  where  it  is  attached  to  the 
diaphragm,  in  the  line  of  the  suspensory  ligament.  The  cut  surface 
of  the  liver  is  granular ;  consistence  tough. 


Cases  of  Xanthelasma.  333 

There  are  three  hydatid  cysts  in  the  liver.  The  largest,  about 
the  size  of  a  cocoa-nut,  occupies  almost  the  entire  thickness  of  the 
right  lobe  of  the  liver;  presses  belov^  on  the  hepatic  ducts  and  on 
the  upper  surface  of  the  liver;  it  is  within  half  an  inch  of  the 
peritonaeum,  and  causes  the  yellow  anaemic  spots  before  mentioned. 
Its  contents  are  colourless  ;  no  daughter  cysts.  Another  cyst,  the 
size  of  an  orange,  lies  immediately  behind  the  first,  and  contains 
shrivelled-up  membranes  and  a  quantity  of  dark  solid  pigment. 
This  cyst  communicates  directly  with  the  hepatic  duct  by  a  short 
canal,  about  half  an  inch  long  and  of  the  diameter  of  a  fourpenny- 
piece.  The  third  cyst  lies  at  the  back  of  the  liver,  and  projects 
to  the  surface  where  the  liver  is  attached  to  the  diaphragm  in  the 
line  of  the  suspensory  ligament.  Its  contents  are  colourless;  no 
daughter  cysts. 

Spleen  large  ;  very  soft.  At  one  end  many  yellow  spots  on 
capsule. 

Kidneys  large ;  cortex  broad,  swollen ;  white  opaque  bundles, 
perpendicular  to  the  medulla,  are  seen  a  amidst  reddish  tissue. 
The  pelvis  and  ureter  of  left  kidney  are  much  dilated. 

Aorta  somewhat  atheromatous;  carotids  and  iliacs  free  from  any 
appearance  of  atheroma  or  xanthelasma. 

The  liver-cells  were  examined  with  the  microscope  within  an 
hour  of  the  liver  being  taken  out  of  the  body.  Specimens  were 
taken  from  many  parts  of  the  right  and  left  lobes.  The  cells 
were  all  found  to  present  the  same  characters.  Their  size  and 
shape  were  not  much  altered,  but  when  seen  in  groups  it  was 
difficult  to  make  out  their  outline.  Their  contents  were  chiefly 
pigment  arranged  around  the  nucleus,  which  was  large  and  con- 
tained nucleoli.  There  were  but  few  fat  granules,  and  no  large 
oil-drops. 

Parts  of  the  liver  were  hardened  in  spirit  and  in  chromic  acid. 
The  increase  of  the  connective  tissue  in  the  portal  canals  was 
certainly  marked,  although  it  was  not  great.  The  connective 
tissue  within  the  lobules  was  not  increased.  There  were  no 
lymphatic  bodies  or  nuclei  present  in  the  connective  tissue.  It 
is  rare  to  see  so  slight  an  increase  in  the  connective  tissue  of  the 
liver  in  cases  of  long-standing  obstruction;  the  slight  increase 
may  be  attributed  to  the  nature  of  the  obstruction,  the  fluid  pressure 
of  hydatid  cyst. 

The  patches  of  xanthelasma  were  hardened  in  spirit,  embedded, 
thin  sections  made  with  a  razor,  coloured  with  carmine  or  logwood 
and  mounted  in  glycerine.  On  examining  them  with  a  low  power, 
the  cuticle  over  the  patches  was  seen  not  to  be  thickened.     In  the 


334  Cases  of  Xanthelasma. 

deeper  layers  ot  the  subcutaneous  connective  tissue  were  seen 
leng-thened  streaks  of  oil  g-lobules.  In  some  specimens  there  was 
an  accumulation  of  oil  around  the  air  follicles,  vessels,  and  other 
structures  passing-  through  the  skin ;  in  others,  not.  These  struc- 
tures, also,  did  not  seem  to  share  in  the  disease.  The  papillae  of 
the  skin  seemed  affected ;  that  is,  the  collection  of  oil  drops  did  not 
enter  the  papilla,  although  it  became  slightly  curved  towards  it,  as 
it  passed  underneath. 

Examined  with  a  higher  power  and  in  preparations  teazed  out 
with  needles,  the  collections  of  fat  drops  were  found  to  contain 
cells  of  various  sizes.  The  smallest  were  not  larger  than  red 
blood-corpuscles;  round,  oval,  rhomboidal,  and  inclined  to  be 
spindle-shaped.  The  smallest  were  free  from  granular  contents 
and  showed  only  one  or  two  nuclei.  Those  larger  were  slightly 
granular.  The  largest  of  all  were  four  or  six  times  the  size  of  the 
smallest;  round,  or  oval  in  shape;  showing  no  nucleus  and  filled 
by  fat,  not  in  many  drops  but  in  one  large  drop,  distending  the 
cells.  The  cells  were  separated  from  one  another  by  fibres  of  the 
connective  tissue,  which  seemed  to  be  scarcely  much  increased. 
Some  of  the  large  fat-containing  cells  had  a  sinuous  appearance, 
their  shape  being  apparently  determined  by  the  fibres. 

The  yellow  patches  under  the  peritonaeum  differed  much  from  the 
patches  of  xanthelasma.  The  spots  were  formed  by  a  spindle- 
shaped  cavity  in  the  connective  tissue  under  the  peritonaeum,  hold- 
ing large  ordinary  fat  cells,  supported  by  an  areolar  network.  The 
patches  under  the  peritonaeum  differed  essentially  from  xanthelasma, 
and  were  mere  local  accumulations  of  fat  in  the  meshes  of  the  con- 
nective tissue  under  the  peritonaeum. 

Jaundice :  Xanthelasma  Palpebrarum. 

Catherine  Lynch,  i8  years  of  age,  came  to  St.  Bartholomew's 
Hospital  on  Oct.  22,  1873,  being  kindly  transferred  to  my  care  by 
my  friend  and  colleague  Dr.  Lauder  Brunton. 

She  came  to  the  Hospital  on  account  of  her  jaundice  which  has 
lasted  over  12  months.  She  came  again  on  Oct.  30,  when  she  was 
questioned  more  at  leisure.  She  then  said  that  she  had  been  ill 
for  2^  years  with  feelings  of  heaviness,  sleepiness,  and  sickliness. 
She  had  noticed  a  swelling  in  the  belly  for  2  years  and  a  month. 
She  had  menstruated  but  once ;  that  about  fourteen  months  ago, 
and  the  discharge  was  then  very  little ;  she  had  enjoyed  tolerably 
good  health  up  to  the  time  of  falling  ill.  She  had  been  jaundiced 
more  than   fourteen   months,  but  the  yellowness  had  been  growing 


Cases  of  Xanthelasma.  335 

less  for  the  last  six  months.  The  urine  brought  was  not  highly 
jaundiced  but  gave  a  distinct  green  ring  with  Gmelin's  test.  Be- 
fore last  week,  she  said,  the  motions  were  yellow ;  this  week  they 
have  been  very  dark. 

Examining  her  more  narrowly,  she  was  found  to  be  only  slightly 
jaundiced.  There  were  two  symmetrical  lines  of  xanthelasma 
along  the  inner  half  of  both  lower  eyelids ;  the  patches  were  oval 
in  shape,  and  their  long  axis  vertical,  smooth  and  soft.  She 
had  noticed  them  for  six  months.  No  other  patches  of  xanthelasma 
were  noticed  over  body  or  hands.  There  was  a  large  phlyctenula 
and  much  injection  of  right  eye.  Also  a  swelling  about  the  size  of 
a  pigeon's  egg,  elastic,  almost  fluctuating,  in  the  left  parotid  region 
had  been  noticed  for  two  years.  The  lymphatic  glands  below  were 
enlarged.  The  left  tonsil  was  enlarged ;  not  so  the  right.  The 
glands  in  the  axilla  enlarged ;  not  in  the  groin.  Blood  examined 
with  microscope  showed  no  increase  of  the  white  corpuscles. 

There  were  many  sonorous  and  sibilant  rhonchi  all  over  chest : 
.cough  very  troublesome ;  phlegm  abundant  and  yellow.  Heart- 
sounds  natural. 

The  liver  was  enormously  enlarged.  Its  edge  was  very  hard 
and  could  be  plainly  felt  in  the  right  iliac  fossa ;  then  the  edge 
began  to  ascend  to  the  right  of  umbilicus;  about  an  inch  above 
which  is  the  notch,  and  the  left  lobe  then  passes  away  along  the 
epigastrium  till  it  be  lost  under  the  ribs.  Surface  of  liver  generally 
smooth ;  but  midway  between  lower  border  of  liver  and  lower  bor- 
der of  ribs  is  a  rounded  swelling  on  surface  of  liver,  smooth  and 
highly  elastic.  Spleen  large  and  moveable.  Belly  tender  when 
handled. 

Father  is  a  porter  at  Covent  Garden.  When  a  child  used  to  eat 
abundantly  of  raw  vegetables;  but  not  lately. 

She  was  told  to  take  a  draught  containing  fifteen  minims  of 
tincture  of  squills,  and  the  same  of  paregoric  in  an  ounce  of  infu- 
sion of  cascarilla  every  four  hours,  and  to  stay  altogether  indoors 
in  a  warm  room. 

She  came  again  on  Nov.  3.  The  cough  was  much  less  although 
she  still  felt  sick  after  a  paroxysm.  The  jaundice  also  less  and 
motions  reported  to  be  a  bright  yellow. 

On  Nov,  6,  the  elastic  tumour  in  parotid  region  seemed  smaller. 
It  was  found  to  be  placed  a  little  behind  the  ear,  more  over  insertion 
of  sterno-mastoid.  There  was  a  swelling  also  not  distinctly  cir- 
cumscribed of  whole  parotid  region,  even  over  the  masseter.  She 
had  never  noticed  any  change  in  power  of  discerning  colours : 
white  things,  for  example,  always  looked  white.     Liver  unaltered. 


33 6  Cases  of  Xanthelasma. 

On  Nov.  10,  the  cough  was  altogether  gone ;  but  the  jaundice 
was  somewhat  deeper :  the  urine  also  gave  a  more  decided  re- 
action with  nitric  acid.  She  was  ordered  to  take  a  draught  con- 
taining dilute  aqua  regia  before  meals. 

On  Nov.  17,  the  jaundice  was  less  marked,  and  there  was  less 
intense  reaction  with  nitric  acid  on  the  urine.  Still  the  jaundice 
was  marked  although  slight. 

It  was  noted  on  Nov.  27,  that  the  elastic  tumour  on  the  liver 
seemed  larger;  it  was  about  the  size  of  half  a  good-sized  orange  ; 
it  was  now  only  a  finger's  breadth  from  the  lower  margin  of  ribs, 
and  stretched  nearer  the  left  edge  of  right  lobe.  Pulse  96,  stand- 
ing. The  phlyctenula  now  began  to  be  more  troublesome,  and  in 
consultation  with  Mr.  Howard  Marsh,  it  was  determined  to  blister 
her  behind  the  ear.  Several  spots  of  erythema  nodosum  were 
noticed  on  arms  and  one  spot  on  shin  ;  but  no  more  xanthelasma. 
To  take  two  teaspoonfuls  of  cod-liver  oil  three  times  a  day. 

On  Dec.  4,  the  eye  was  better :  the  liver  as  before. 

On  Dec.  11,  the  eye  was  again  not  so  well.     She  was  therefore, 
sent  to  see  Mr.  Power,  the  Ophthalmic  Surgeon,     Since  that  time, 
I  have  not  seen  her  nor  have  I  been  able  to  gather  any  information 
about  her. 


Jaundice :  Xanthelasma  Multiplex. ^^ 

Mrs.  C.  aged  36,  was  an  out-patient  at  S.  Bartholomew's  Hos- 
pital under  Dr.  Andrew  in  the  spring  of  1868. 

The  patient  has  been  married  17  years.  She  has  had  9  children, 
the  youngest  14  months  old,  one  is  dead.  She  has  had  3  miscar- 
riages. Two  years  ago  last  December  she  had  a  quarrel  with  her 
husband  and  a  very  great  fright ;  and  about  a  week  after,  she 
began  to  turn  yellow.  They  were  then  living  near  Aberdeen,  and 
it  would  seem  that  she  had  had  much  anxiety  and  annoyance  for 
some  time  before.  For  the  last  three  years  she  had  been  subject 
to  flooding.  The  spots  began  to  appear  about  six  months  ago,  and 
were  first  noticed  on  the  elbows  as  little  spots  the  colour  of  the 
skin.  She  has  had  much  itching  and  irritability  of  the  skin,  which 
came  on  about  two  months  after  the  jaundice  but  is  not  nearly  so 
bad  now.  At  one  time  she  used  to  be  obliged  frequently  to  sponge 
in  cold  water,  and  could  not  sleep  at  night.  The  spots  are  most 
abundant  on  the  elbows,  palms,  and  soles ;  but  on  the  palms,  (soles 

•  This  case  has  been  published  before  in  Trans,  of  Path.  Sue.  of  Lundon,  1874, 
Vol.  XXV.  p.  259. 


Cases  of  Xanthelasma.  337 

not  seen)  they  are  very  slig-htly,  if  at  all  elevated,  resembling  rather 
opaque  spots  in  the  skin,  which  presents  a  marbled  appearance 
from  the  very  great  number.  She  does  not  sleep  well,  but  does 
not  know  why.  The  tongue  is  clean  :  the  appetite  uncertain  ;  she 
used  to  be  fond  of  fat,  but  cannot  take  it  now.  The  bowels  are 
regular,  slightly  costive.  Motions  during  illness  have  been  light 
coloured,  but  for  the  last  three  weeks,  they  have  been  almost 
natural.  The  urine  is  said  to  be  high  coloured.  The  pulse  is  60. 
She  has  lost  nearly  four  stone  in  weight,  she  used  to  weigh  four- 
teen stone. 

Two  or  three  weeks  ago  she  passed  something  hard  at  stool, 
(?  gallstone),  and  her  present  improvement  seems  to  date  from 
that.  Her  complexion  is  now  lighter  and  the  spots  are  less  than 
they  were  a  few  weeks  ago, 

yaundice :  Xanthelasma  Multiplex. 

James  Piggott,  aged  32,  came  to  Saint  Bartholomew's  Hospital 
Sept  24,  1873. 

He  says  he  is  unmarried,  but  that  he  has  never  had  syphilis  or 
gonorrhoea.  He  has  been  a  teetotaler  since  1863.  He  has  always 
enjoyed  good  health;  in  18  years  he  has  only  been  away  from 
business  2  hours  owing  to  ill-health. 

He  has  been  jaundiced  now  for  three  months.  He  has  been  over 
anxious  of  late  about  business. 

Present  state.  The  colour  of  the  skin  is  a  deep  sallow  unlike 
ordinary  jaundice  :  the  conjunctivae  are  blood-shot,  and  do  not  at 
first  sight  strike  observer  as  being  icteric.  On  close  examination 
they  are  plainly  so.  The  urine  high  coloured,  but  contains  no  al- 
bumen, and  on  being  tested  with  nitric  acid  in  Gmelin's  way,  there 
is  no  trace  of  a  green  colour,  nothing  but  a  red  ring  above  the  nitric 
acid  is  found.  The  stools  are  said  to  be  now  of  a  fawn  colour ; 
under  the  club  doctor  they  were  dark.  Liver  dulness  (absolute) 
begins  two  fingers'  breadth  below  nipple  and  reaches  down  to  the 
level  of  the  umbilicus.  The  liver  can  be  felt  below  this :  it  does 
not  cross  middle  line.  It  is  slightly  tender  to  feel :  its  surface 
smooth,  save  just  below  the  junction  of  the  ribs  and  cartilages, 
where  a  rounded  smooth  swelling  size  of  a  small  apple  may  be 
felt.  The  belly  somewhat  retracted  :  not  tender  generally.  The 
pulse  is  18  in  15",  intermittent  about  i  in  18, 

There  is  much  itching  especially  about  the  thighs  at  night.  He 
does  not  complain  of  any  pain.  His  chief  trouble  is  his  weakness 
and  loss  of  flesh. 

To  take  the  nitro-muriatic  acid  draught. 

z 


338  Case  of  Spontaneous  Recovery 

Oct.  8.  Liver  dulness  as  before.  Epig-astrium  slightly  tender. 
The  splenic  dulness  is  enlarged  and  the  tip  can  be  distinctly  felt 
under  ribs.  Pulse  22  in  15",  not  intermittent  but  very  small. 
There  is  no  murmur  at  heart;  •  second  sound  at  base  reduplicated. 
Weight  remains  about  the  same. 

Oct.  1 1.  The  edge  of  the  liver  is  rounded  to  feel ;  motions  of  a 
light  yellow  colour.  The  conjunctivae  are  now  markedly  jaun- 
diced ;  the  urine  bilious,  but  contains  no  albumen.  A  beautiful 
green  reaction  is  given  with  Gmelin's  test. 

Oct.  15.  He  ate  two  pears  yesterday  and  has  been  much 
purged ;  does  not  feel  so  well  in  consequence.  Jaundice  the  same. 
There  is  no  xanthelasma  palpebrarum. 

Oct.  29.  Epigastrium  still  tender.  Liver  dulness  as  before ; 
edge  as  before ;  the  rounded  swelling  as  before.  Jaundice  some- 
what less.  Pulse  18  or  19  in  15".  The  urine  shows  no  albumen, 
but  a  slight  green  reaction  with  nitric  acid.  There  is  no  xanthe- 
lasma to  be  seen  anywhere.  The  man  says  he  feels  stronger; 
tongue  very  red,  cracked  across.  He  goes  to-morrow  to  St.  Ives 
to  live. 

Dec.  3.  He  came  up  to-day  from  St.  Ives,  where  he  has  been 
for  the  last  six  weeks.  He  says  he  has  gained  2  or  3  lb.  in  weight, 
but  he  still  complains  of  itching  ;  the  jaundice  is  now  only  slightly 
marked;  the  urine  on  the  other  hand  very  highly  coloured ;  on 
boiling  and  adding  nitric  acid  a  faint  cloud  appears;  there  is  deep' 
green  reaction  with  nitric  acid.  There  is  a  general  bulging  of  the 
lower  ribs  on  the  right  side.  The  deep  liver  dulness  begins  at 
nipple,  but  is  not  absolute  for  two  fingers'  breadth  below.  The 
dulness  now  extends  below  ribs  for  three  fingers'  breadth.  Tym- 
panitic sound  to  the  left  of  the  middle  line.  The  liver  can  be  felt 
almost  to  level  of  umbilicus.  Tip  of  spleen  also  distinctly  felt. 
Pulse  20  in  15",  not  intermittent.     Stools  now  light  drab. 

Has  noticed  no  changes  in  perception  of  colours  since  illness. 
The  conjunctivae  are  much  injected.  A  few  yellow  spots  size  of 
pin's  point  around  inner  canthus  of  eyes. 

To  continue  the  draught  of  nitro-muriatic  acid. 

Aug.  12,  1876.  He  came  to  see  me  again.  For  several  months 
past  he  has  been  living  in  North  Staffordshire,  working  at  the  pot- 
tery business.     He  is  in  London  for  the  day. 

He  has  now  well  marked  xanthelasma  multiplex.  There  are 
large  symmetrical  patches  on  the  inner  aspect  of  both  eyelids  of 
the  plane  variety.  On  the  upper  right  eyelid  is  a  tuberose  patch 
size  of  a  pea.  There  is  none  on  the  face  or  head,  if  a  doubtful  spot 
on  the  lower  lip  be  excepted.     None  on  front  or  back  of  trunk, 


from  Xanthelasma  Multiplex.  339 

until  the  cleft  of  the  nates  be  reached;  on  each  side  of  the  upper 
part  of  this  cleft  is  an  abundant  crop  of  prominent  tuberose  xan- 
thelasma. In  the  middle  line  of  the  sacrum  there  is  an  oblong 
patch  of  xanthelasma  planum.  On  the  arms  there  is  none,  save 
about  both  elbows ;  the  olecranal  surface  is  studded  with  the 
tuberose  form ;  the  flexure  with  the  plane.  There  is  one  small 
tuberosity  on  back  of  right  hand;  the  flexures  of  both  palms  and 
of  the  fingers  are  marked  by  broadish  lines  of  linear  xanthelasma. 

There  is  a  patch  of  plane  xanthelasma  at  base  of  penis  and 
another  in  middle  line  of  perinaeum.  There  is  none  on  the  thighs 
and  legs.  But  on  the  left  sole,  just  where  the  great  toe  joins  the 
foot,  is  a  streak  of  linear  xanthelasma. 

There  is  no  xanthelasma  on  tongue;  nor  as  far  as  can  be  judged 
on  gums.     He  wears  false  teeth. 

He  has  been  slightly  jaundiced  since  his  last  visit.  He  scratches 
his  thighs  much,  but  says  this  is  due  more  to  habit  than  real  sense 
of  itching.  Conjunctivae  still  coloured  yellow  ;  but  the  complexion 
is  very  peculiar,  not  jaundiced,  but  very  dark  ;  in  a  healthy  person 
it  would  suggest  an  infusion  of  black  blood.  He  has  black  hair. 
The  urine  is  high  coloured  and  looks  bilious.  It  does  not  stain 
white  paper  yellow,  nor  does  it  give  a  green  colour  with  nitric 
acid.     After  being  boiled,  nitric  acid  causes  an  opalescence. 

He  says  he  first  began  to  notice  the  xanthelasma  in  his  hands, 
the  spring  of  this  year ;  he  does  not  remember  in  what  month. 
He  thought  they  were  due  to  the  cold  weather.  He  has  been  jaun- 
diced continuously  for  three  years. 

The  liver  dulness  now  begins  two  fingers'  breadth  below  nipple 
and  reaches  to  a  finger's  breadth  above  border  of  chest.  In  axil- 
lary line  it  reaches  to  border  of  chest.  It  cannot  be  felt,  neither 
can  spleen.  The  tongue  is  red  and  fissured.  The  appetite  is  bad. 
He,  however,  considers  himself  stronger  and  better  than  he  was 
three  years  ago. 

He  was  heard  from  on  Jan.  4,  1877:  he  said  :  "The  white  marks 
upon  my  hands  are  less  plain,  but  I  have  such  a  habit  of  rubbing 
myself  and  rubbing  off  any  little  scar  or  head  which  are  (sic)  felt 
moist  when  warm," 

Oct.  18,  1879.  ^6  again  reported  himself  to  day.  He  is  still 
slightly  jaundiced  and  looks  thin.  He  is  able  to  do  some  light 
work,  such  as  that  of  a  clerk  or  book-keeper. 

The  patches  of  xanthelasma  have  everywhere,  save  on  the  eye- 
lids, disappeared.  The  palms  of  the  hands,  the  elbows,  the  nates 
and  sacrum,  penis  and  perinaeum,  and  the  left  toe,  are  free  from 
all  traces  of  the  disease.     The  skin  is  quite  smooth  and  supple, 

Z2 


340  Recovery  from  Xanthelasma. 

and  it  is  hard  to  believe  that  it  has  been  the  seat  of  so  extensive  a 
patholog-ical  change.  Over  the  elbow  there  is  some  roughness, 
but  it  is  doubtful  whether  it  be  more  than  is  common ;  and  there 
are  one  or  two  scars,  caused,  he  says,  by  his  tearing  the  tubercles 
out  with  his  nails,  which  then  bled  plentifully. 

He  cannot  remember  the  exact  time  at  which  the  patches  began 
to  go  away,  but  thinks  it  was  about  the  beginning  of  1877.  No 
treatment  was  adopted  with  a  view  to  their  removal. 

There  is  still  the  same  marked  bulging  of  the  lower  right  ribs, 
and  the  liver's  thin  edge  can  be  felt  just  under  the  margin  of  the 
ribs ;  the  spleen  can  also  be  distinctly  felt.  The  liver  dulness  be- 
gins three  fingers'  breadth  below  nipple  line,  and  at  the  same  dis- 
tance in  parasternal  line,  but  very  quickly  is  succeeded  by  a 
tympanitic  sound. 

The  urine  is  still  bilious  to  the  eye,  but  gives  no  distinct  Gmelin's 
reaction. 


CHAPTER   XIII. 

The  Morbid  Anatomy  of  Jaundice. 

The  body  of  a  person  who  has  died  of  jaundice  very 
readily  decomposes.  Even  in  cold  weather,  the  veins 
over  the  belly  and  thighs  may  be  seen  as  purple  streaks 
within  24  hours  of  death.  The  rigor  mortis  rapidly  dis- 
appears. 

The  jaundice  of  the  tissues  noticed  during  life  per- 
sists after  death.  Gubler  thinks  that  it  is  the  fibrous 
tissues  only  which  become  stained  in  jaundice  by  a  sort 
of  elective  affinity,  like  that  of  madder  for  young  bones.* 

Certain  tissues  remain  free  from  colour  even  in  the  most 
intense  jaundice.  Such  are :  the  teeth,  the  hair,  the  brain, 
the  humours  of  the  eye,  the  cartilages,  an  appearance 
which  may  specially  be  noticed  in  the  costal  cartilages  ; 
not  so  well  marked  when  the  body  is  first  opened,  but 
it  may  well  be  seen  when  the  bile  pigment  in  the  ribs 
has  been  oxydised  by  the  action  of  the  air  into  biliver- 
din  ;  the  cartilages  remaining  whitish,  while  the  ribs 
are  deep  green.  The  absence  of  colour  in  the  teeth 
and  cartilages  may  be  readily  explained  by  the  absence 
of  large  blood-vessels  in  their  structure.  It  is  not  so 
easy  to  explain  the  absence  of  colour  from  the  nerve- 
centres  and  nerves  themselves,  which  are  always  white. f 
The  fluid  in  the  meninges  and  in  the  ventricles  of  the 
brain  may  be  deeply  yellow,  while  the  substance  of  the 
brain  itself  is  free  from  colour. 

*  Gubler,  in  Michel,  De  Victere  hemapheiqiie,  These  de  Paris,  1868.  p.  8. 

f  Dr.  Murchison  [Lectures  on  Dis.  of  the  Liver,  London,  i858.  p.  285)  says  that 
the  jaundiced  tint  penetrates  the  brain.  This  is  quite  contrary  to  my  own  experi- 
ence and  to  the  statements  of  nearly  every  other  writer  that  I  have  consulted. 
Frerichs  indeed  says  that  the  brain,  when  cedematous,  may  have  a  yellowish 
appearance,  but  this  is  clearly  due  to  the  unnatural  presence  of  serum  in  the  brain, 
not  to  the  colour  of  the  brain  itself. 


342  Method  of  Examining  the. 

It  is  worthy  of  note  that  in  some  cases  of  secondary 
maHgnant  tumours  in  the  Hver,  where  the  primary  tu- 
mour, such  as  cancer  of  the  head  of  the  pancreas,  has 
caused  a  jaundice,  the  secondary  tumours  in  the  Hver 
are  not  stained,  though  in  the  midst  of  a  highly  jaun- 
diced organ.  This  fact  may  be  compared  with  the 
same  absence  of  colour  in  the  fluid  of  the  gall  bladder 
and  gall  ducts  after  long-standing  obstruction. 

In  jaundice  the  first  organ  to  suffer  is  the  liver  and 
its  ducts,  and  to  this  part  of  the  body  the  attention  of 
the  morbid  anatomist  must  be  at  first  directed.  It  is  of 
the  utmost  importance,  as  Virchow  has  pointed  out,* 
that  the  examination  of  the  ducts  leading  from  the  liver, 
the  hepatic  and  common  duct,  should  be  made  in  a 
particular  fashion,  otherwise  the  results  gained  are  of 
little  or  no  value.  The  object  of  the  examination  is 
to  test  the  patency  of  the  common  duct.  This  used 
formerly  to  be  done  by  opening  the  duodenum  near  the 
orifice  of  the  common  duct,  and  then  pressing  upon  the 
gall  bladder.  If  the  contents  of  the  gall  bladder  passed 
into  the  duodenum,  the  ducts  were  judged  to  be  patent 
during  life.  This  test  is  exceedingly  rough,  and  cannot 
be  trusted  either  for  negative  or  positive  results.  In 
the  first  place,  if  no  bile  flow  out,  it  does  not  show  that 
the  common  duct  is  obstructed,  as  the  cystic  duct  may 
be  plugged,  and  thus  no  bile  from  the  bladder  may  pass 
into  the  gut ;  in  the  second  place,  if  bile  flow  out,  it 
does  not  show  that  there  was  no  obstruction  during 
life,  as  catarrh,  hyperaemia,  and  oedema,  of  the  mucous 
membrane  of  the  common  duct  readily  enough  disappear 
after  death,  while  during  life  a  serious  obstruction  may 
have  existed.  Lastly,  it  does  not  exclude  obstruction 
of  the  hepatic  duct. 

The   same  objections  may  be  made  to  the  passing  of 

*  Virchow,  Arch.  f.  path.  Anat.  1865.  Bd.  xxxii.  p.  117.  Cf.  Wicn.  mcd.  Wochen- 
schrift,  1858  No.  24. 


Ducts  in  Cases  of  Jmmdice.  343 

a  probe  up  the  duct  from  the  papilla,  and  seeing  if  there 
be  any  obstruction  which  cannot  be  overcome.  An 
improvement  on  both  the  foregoing  methods  is  the  plan 
of  laying  the  duct  open,  and  seeing  if  any  gross  ob- 
struction, such  as  a  plug  of  mucus,  or  tumour  pressing 
on  the  duct,  exist.  But  in  all  cases,  however,  the  fol- 
lowing will  be  found  a  better  way :  in  opening  the  belly 
great  care  must  be  taken  not  to  disturb  or  press  on  the 
gall  bladder  or  ducts.  The  large  intestine  and  omen- 
tum may  be  carefully  removed,  and  raising  the  liver 
without  pressing  on  the  gall  bladder,  the  common  and 
hepatic  ducts  may  now  be  dissected  out.  It  is  most 
convenient  to  open  the  common  duct  a  little  above  its 
passage  into  the  duodenum,  and  with  a  probe-pointed 
pair  of  scissors  to  follow  it  first  downward  into  the  gut, 
and  then  upwards  towards  the  liver.  Great  attention 
must  be  paid  to  three  points  in  the  state  of  the  duct:  i.  a 
swollen  state  of  the  mucous  membrane  ;  it  is  well  known 
that  hyperaemia  of  mucous  membranes  readily  disap- 
pears after  death,  just  as  the  redness  of  erysipelas  of 
the  skin  is  lost,  and  the  only  post  mortem  signs  are  the 
swelling  and  oedema  :  ii.  a  plug  of  mucus  and  epi- 
thelium at  the  opening  of  the  duct  into  the  intestine  ; 
if  this  be  white  and  not  stained  by  bile,  it  is  proof  that 
no  bile  has  passed  along  the  duct  since  the  plug  was 
formed :  iii.  a  colourless  state  of  the  lower  part  of  the 
duct  near  the  intestine,  while  the  upper  part  is  stained 
yellow  by  bile.  This  is  most  important  evidence,  as  it 
shows  that  no  bile  has  passed  down  that  part  of  the 
duct  which  is  unstained  by  bile,  at  all  events  for  several 
days  before. 

I  have  sometimes  found  that  the  mere  movement  of 
the  body  after  death,  such  as  is  necessary  in  carrying  it 
from  one  room  to  another,  is  enough  in  some  cases  of 
jaundice  to  send  the  bile  from  the  gall-bladder  down 
the  ducts.     Some  time  ago  I  was   examining  a  case  of 


344  Dilatation  of  the  Bile  Ducts 

pneumonia  complicated  by  jaundice,  and  used  great 
care  that  no  pressure  should  be  made  on  the  gall- 
bladder. Yet  on  opening  the  ducts,  common  and  he- 
patic, thev  were  found  deeply  stained  with  a  fluid  of  the 
same  colour  and  appearance  as  that  in  the  gall-bladder; 
no  obstruction  was  found  in  the  ducts  or  at  the  papilla. 
The  contents  and  mucous  membrane  of  the  duodenum 
were  stained  yellow  for  about  three  inches  above  and 
below  the  papilla ;  but  beyond  this  narrow  strip,  the 
contents  and  wall  of  the  intestine,  above  and  below, 
were  perfectly  free  from  all  bile  staining.  The  con- 
tents of  the  small  intestine  were  markedly  colourless. 

The  obstruction  to  the  ducts  may  also  be  high  up  in 
the  liver  in  the  finer  ducts,  so  that  they  should  be  care- 
fully dissected,  and  an  obstruction  within  them  may  be 
discovered.  Oskar  Wyss*  and  Ebsteinf  have  shown 
the  existence  of  plugs  of  mucus  in  the  fine  ducts  of  the 
liver  in  cases  of  poisoning  by  phosphorus,  in  which 
disease  the  large  ducts  of  the  liver  are  commonly  free 
and  coloured.  Cornil  has  shown  that  even  the  finest 
ducts,  those  just  outside  the  lobules,  may  be  filled  by 
masses  of  epithelium,  and  obstruction  to  the  flow  of 
bile  caused  in  this  manner.  J 

If  the  obstruction  to  the  bile  ducts  be  permanent  and 
near  the  duodenum,  as,  for  example,  a  tumour  growing 
from  the  head  of  the  pancreas,  the  ducts  outside  the 
liver  are  commonly  found  much  dilated.  The  gall- 
bladder suffers  very  early  and  becomes  much  dis- 
tended. The  ducts  themselves  may  often  be  seen 
as  large  as,  or  even  larger  than,  the  middle  finger. 
In  man  they  do  not  seem  to  become  tortuous  ;  but  it  is 
not  uncommon  to  see  this  appearance  in  animals  when 
the   ducts  have   been  tied   near  the  duodenum.     They 

*  Oskar  Wyss,  Arch.  d.  Heilkunde,  1867,  p.  469. 

f  Ebstein,  ibid.  1867,  p.  506,  and  1869,  p.  379. 

J  Cornil,  Comptes  rendits  dcs  seances  de  la  Societe  de  Biologic,  1875,  juillet,  p.  306. 


from  Permanent  Obstruction.  345 

may  attain  an  enormous  size.  As  an  instance  of  this, 
there  is  a  case  which  has  become  quite  classical,  be- 
cause quoted  by  Morgagni.  It  is  a  case  by  Traffelmann, 
who  found  in  the  body  of  Daniel,  Archbishop  of  Mainz, 
that  the  bile  ducts  were  filled  with  gall-stones  and  dilated 
instarutricnli*  Morgagni,  in  quoting  this,  has  changed 
the  utriculi  into  ventriculi,f  and  every  writer  up  to  the 
present  day  has  quoted  this  case  as  one  of  dilatation  of 
the  bile  ducts  to  the  size  of  a  stomach.  There  are, 
however,  well  authenticated  cases  in  which  the  dilata- 
tion of  the  ducts  has  been  quite  as  great,  if  not  greater, 
than  that  imagined  by  Morgagni.  The  most  extreme 
case  with  which  I  am  acquainted  is  recorded  by  Dr.  Hal- 
liday  Douglas.  In  a  jaundiced  girl,  seventeen  years  of 
age,  a  fluctuating  tumour  could  be  felt  on  the  right  side 
nearly  as  low  as  the  ilium.  Thirty  ounces  of  fluid  were 
withdrawn  by  tapping.  On  examination  after  death,  a 
sac  was  found  on  the  right  side  of  the  belly,  over  the 
front  wall  of  which  the  duodenum  passed  as  a  flat  band. 
The  walls  of  the  sac  were  dense  and  fibrous,  one  twelfth 
to  one  eighth  of  an  inch  in  thickness.  At  the  upper 
part  of  the  sac,  the  dilated  openings  of  the  hepatic  and 
cystic  ducts  were  seen.  The  hepatic  duct  within  the 
liver- was  much  dilated.  J 

Todd,  of  Dublin,  found  in  a  girl  of  14,  the  hepatic 
and  common  ducts  so  enormously  dilated  that  they 
contained  more  than  a  quart  of  bile,  and  formed  a  sac 
which  reached  from  the  porta  of  the  liver  to  the  os 
sacrum.  The  ducts  lay  behind  the  duodenum,  pan- 
creas, and  the  root  of  the  mesentery,  and  covered  the 

*  Traffelmann,  quoted  by  Schenk,  Obs.  med.  lib.  iii.  sect.  ii.  Lugd.  1644,  p.  405. 
To  increase  the  confusion,  the  Archbishop  is  often  spoken  of  as  a  Prince:  it  must 
be  remembered  that  the  Archbishops  of  Mainz  were  temporal  as  well  as  spiritual 
princes.  He  was  the  first  of  the  electoral  college  of  the  Roman  Empire,  and  Arch- 
chancellor  of  Germany. 

f  Morgagni,  De  scdibits,  etc.  Epist.  xxxvii.  Sect,  xlvii. 

+  Halliday  Douglas,  Motitlily  Jotirnal  of  Medical  Science,  Edinburgh,  1S52,  Vol. 
xiv.  p.  97. 


346  Histology  of  the  Dilated  Ducts. 

anterior  surface  of  the  right  kidney  and  the  greater  part 
of  the  left.  The  cause  of  the  dilatation  was  a  scirrhous 
state  of  the  pancreas.* 

Frerichs  gives  a  drawing  of  an  immensely  dilated 
common  duct,  which  is  in  the  Museum  at  Breslau.*]* 

The  ducts  within  the  liver  suffer  latest.  They  do 
not  dilate  to  anything  like  the  size  of  those  outside. 
This  is  doubtless  due  to  the  liver-tissue  preventing  any. 
very  great  dilatation. 

The  ducts  may  show  uniform  or  saccular  dilatations. 
The  former  is  no  doubt  the  most  common.  The  left 
hepatic  duct  has  always  appeared  to  me  more  dilated 
in  proportion  to  its  size  than  the  right.  This  is  pro- 
bably due  to  the  bulk  of  the  left  lobe  being  less  than 
the  right ;  thus  less  resistance  to  the  dilating  force  is 
offered. 

The  walls  of  the  ducts  themselves  are  thickened,  even 
to  the  naked  eye.  Under  the  microscope  this  thicken- 
ing is  seen  to  be  due  to  a  great  overgrowth  of  the  fibrous 
coat.  In  this,  great  abundance  of  lymphatic  elements 
may  be  found,  just  as  in  cirrhosis.  Raynaud  and 
Sabourin  have  lately  described  as  well  distinct  layers 
of  muscular  tissue  in  the  walls  of  the  dilated  ducts 
outside  the  liver  ;  but  the  muscular  tissue  disappeared 
as  soon  as  the  ducts  passed  into  the  liver  itself.J 
Frerichs§  and  Schafer||  have  been  unable  to  recog- 
nise any  epithelium  on  these  dilated  ducts.  Heinrich 
Mayer,^  however,  speaks  of  them  ;    and  I  myself  have 

*  Todd,  Dublin  Hospital  Reports,  1817,  Vol.  i.  p.  325.  It  is  worthy  of  note,  as 
some  explanation  of  the  enormous  dilatation  of  the  common  and  hepatic  ducts,  that 
in  both  these  cases  of  Halliday  Douglas  and  of  Todd,  the  cystic  duct  was  obstructed. 
In  Frerichs'  case,  the  gall-bladder  was  of  the  usual  size. 

t  Frerichs,  Klinik  dcv  Lcberkmnkhcitcn,  Braunschweig,  1861,  Bd.  ii.  p.  444.  He 
has  used  symbols,  so  it  is  almost  impossible  for  an  Englishman  to  tell  what  he 
means  by  his  measurements. 

X  Maurice  Raynaud  and  Charles  Sabourin,  Archives  de  Physiologic,  1879,  p.  46. 

%  Frerichs,  op,  cit.  Bd.  i.  p.  148. 

II  Schiifer,  De  hydropc  dtictuum  biliarium.  Diss.  Inaug.  Turic.  1842,  p.  g. 

II  Heinrich  Mayer,  Mcdiz.  Jahrbb.  hrsgcg.  von  d.  k.k.  Gcscllschaft  der  Acrzte, 
Wicn,  1872,  p.  139. 


Histology  of  the  Dilated  Ducts.  347 

seen  abundance  of  cylindrical  epithelium  in  cases  which 
I  have  examined  carefully.  Charcot  and  Gombault  seem 
to  consider  the  retention  of  the  epithelium  almost  a  neces- 
sary feature  in  the  anatomy  of  the  dilated  ducts ;  the 
epithelial  proliferation,  say  they,  must  be  very  active, 
and  is  a  sign  of  the  irritated  state  of  the  wall  of  the 
duct.*  I  have  little  doubt  that  the  absence  of  the  epi- 
thelium is  a  post-mortem  change  ;  the  ducts  must  not  be 
meddled  with  before  the  examination  ;  they  must  not 
be  washed  or  wiped,  or  no  epithelium  will  be  found. 

The  follicles  which  open  upon  the  mucous  surface  of 
the  gall  ducts  are  usually  found  dilated  and  filled  with 
pigment.  Raynaud  and  Sabourin  have  paid  especial 
attention  to  the  appearance  of  these  follicles  in  obstruc- 
tion to  the  ducts.  They  find  in  the  connective  tissue  of 
the  portal  canals  numerous  little  bodies,  which  resemble 
the  section  of  small  racemose  glands,  and  are  scattered 
without  order  around  the  bile  ducts.  They  are  made 
up  of  tortuous  tubules  lined  with  a  single  layer  of  cubi- 
cal epithelium,  and  opening  into  the  larger  bile  ducts. 
Raynaud  and  Sabourin  look  upon  these  bodies  as  either 
the  normal  glands  of  the  ducts  much  hypertrophied,  a 
view  which  seems  to  me  the  more  probable  ;  or  else 
that  the  very  small  ducts  seen  naturally  in  the  portal 
spaces,  are  prolonged  and  rolled  up  into  a  ball.f  They 
appear  to  be  quite  distinct  from  the  developments  of  the 
ducts  described  by  Charcot  and  Gombault,  Hanot  and 
others. 

The  contents  of  the  widened  ducts  vary  much.  If  the 
examination  be  made  soon  after  the  obstruction  have  been 
set  up,  the  contents  will  be  found  to  be  bile  little  altered. 
Later  on,  the  bile  becomes  thickened  and  tenacious,  and 
a  kind  of  biliary  gravel  is  thrown  down.  Should  the  ob- 
struction continue  long,  the  colouring  matters  of  the  bile 

*  Charcot  and  Gombault,  Archives  de  Physiologic,  1876,  pp.  275  and  289. 
f  Raynaud  and  Sabourin,  op.  cit.  pp.  43  and  48. 


348  Cheinistry  of  Fluid  in  Bile  Ducts. 

are  absorbed  and  leave  only  a  colourless  fluid,*  at  first 
viscid  from  the  presence  of  mucus,  but  afterwards  limpid. 
This  colourless  fluid  has  been  very  little  examined.  There 
are  but  few  records  of  the  analysis  of  the  colourless  fluid 
found  in  the  gall-bladder,  but  there  seems  to  be  only 
one  case  recorded  of  any  chemical  analysis  of  the  fluid 
from  the  ducts.  In  this  case  Schafer  says  it  possessed 
all  the  physical  and  chemical  properties  of  the  plasma 
of  the  blood. t  In  two  cases  which  I  have  examined  I 
found  no  bile  acids  or  bile  pigment  in  the  fluid. 

The  presence  of  this  colourless  fluid  was  formerly 
looked  upon  as  evidence  of  the  cessation  of  the  secre- 
tion of  bile,  of  an  acholia,  an  opinion  which  even  a 
recent  writer  has  supported. {  The  phasnomena  are, 
however,  better  explained  by  believing  that  the  fine 
ducts  of  the  liver  have  been  blocked  up  by  mucus,  and 
thus  the  bile  hindered  descending  into  the  larger  tubes. 

The  saccular  dilatations  of  the  ducts,  and  the  multi- 
ple abscesses  of  the  liver,  sometimes  caused  by  obstruc- 
tion to  the  ducts,  would  best  be  considered  under  the 
head  of  diseases  of  the  ducts  themselves. 

The  state  of  the  texture  of  the  liver  itself  will  next  be 
considered.  Soon  after  the  obstruction  to  the  ducts  is 
set  up,  the  liver  changes  in  colour.  In  some  cases  of 
short  duration,  however,  no  change  in  colour  is  seen. 
The  liver  becomes  mottled  in  two  shades  of  yellow,  of 
which  the  deeper  colour  is  seen  in  the  centre  of  the 
lobules,  the  lighter  in   the  circumference.     Under  the 


•  I  fear  that  I  am  unable  to  agree  with  Dr.  Hilton  Fagge  in  his  statement  that 
'  in  jaundice  the  biliary  passages  are  almost  always  found  to  contain,  not  bile,  but, 
an  almost  colourless  mucus."  {Guy's  Hasp.  Reports,  1875,  Vol.  xx.  Third  Series, 
p.  172).     In  my  own  experience  the  reverse  has  been  the  case. 

f  Schafer,  loc.  cit.  The  absence  of  bile  acids  from  the  bile  found  after  death  in 
the  gall-bladder  would  seem  to  be  more  common  than  is  generally  supposed. 
Golowin  {Arch.  f.  path.  Aunt.  1871,  Bd.  liii.  p.  420.)  says  that  in  two  out  of  36 
cases,  no  bile  acids  could  be  found :  both  were  cases  of  parenchymatous  degenera- 
tion of  the  liver  and  one  was  jaundiced. 

J  Moxon,  Trans,  of  the  Pathological  Society  of  London,  1873,  Vol.  xxiv.  p.  129. 


Absorption  of  Bile  in  Jaundice.  349 

microscope  the  mottling  is  seen  to  be  due  to  an  infiltra- 
tion of  the  cells  of  the  liver  with  granules  of  pigment, 
the  pigment  being  most  abundant  in  the  centre  of  the 
acinus  around  the  hepatic  vein.  I  am  not  acquainted 
with  any  explanation  of  the  appearance  of  bile  pigment 
in  the  cells  of  the  centre  rather  than  of  the  circumfer- 
ence. It  has  seemed  to  me  possible  that  as  the  gall- 
ducts  take  their  rise  from  the  circumference  of  the 
lobule,  the  cells  lying  nearest  to  them  may  be  able  to 
discharge  their  contents  more  readily  than  the  cells 
lying  in  the  deeper  parts. 

In  one  of  his  experiments  on  the  bile,  Heidenhain 
allowed  a  solution  of  indigo-sulphate  of  soda  to  flow 
under  moderate  pressure  into  the  bile  duct  of  a  living 
animal.  He  found  the  mucous  membranes,  the  con- 
junctiva, the  serous  membranes,  andthe  fasciae  to  become 
blue  ;  and  even  blue  urine  was  passed.  But  the  liver 
itself  was  the  organ  least  coloured.  By  careful  observ- 
ation it  could  be  seen  that  here  and  there  between  the 
lobules  there  was  a  tinge  of  colour  ;  the  lobules  them- 
selves being  natural.  If,  at  the  end  of  the  experiment, 
the  liver  were  hardened  and  examined,  only  the  intra- 
lobular bile  ducts  and  their  neighbourhood  were  found 
coloured.  And  if  the  experiment  were  broken  off,  even 
where  the  conjunctivae  and  urine  had  become  blue,  the 
liver  recovered  itself  and  clear  bile  was  secreted.  These 
circumstances  make  it  evident,  says  Heidenhain,  that 
absorption  does  not  take  place  within  the  canals  of  the 
lobule  in  which  the  bile  is  secreted,  or  otherwise  the 
liver  would  be  quite  blue  ;  the  intra-lobular  ducts  of 
Chrzonszczewsky*  would  be  then  coloured ;  but  the 
absorption  must  take  place  in  the  inter-lobular  ducts. 
The  place  of  absorption  is  therefore  different  to  the 
place  of  secretion.  The  first  takes  place  between  the 
lobules,  the  second  within  them.      When  in  jaundice 

*  Chrzonszczewsky,  Arch.  f.  path.  Anat.  1866.  Bd.  xxxv.  p.  153. 


350  A  bsorption  of  Bile  in  Jaundice. 

the  liver  cells  become  coloured,  it  is  a  secondary  not 
a  primary  phaenomenon,  the  bile  is  secreted  by  the 
lobules,  passed  into  the  intra-lobular  ducts  and  thence 
into  the  inter-lobular  ducts,  through  the  walls  of  which 
it  is  absorbed,  and  passes  by  way  of  the  lymphatics 
again  into  the  lobules.* 

The  readiness  with  which  bodies  are  absorbed  from 
the  bile  ducts  is  shown  by  the  following  experiment  by 
Picard.  He  injected  a  solution  of  "prussiate  of  potash" 
into  the  stomach  of  two  dogs  in  full  digestion,  but  the 
injection  was  followed  by  no  symptoms  of  poisoning. 
The  same  drug,  injected  into  the  bile  duct,  caused  the 
death  of  the  animal  instantly.  It  is  perhaps  worthy  of 
note,  that  no  resistance  was  felt  to  this  injection,  but 
that  it  passed  as  readily  as  into  an  empty  cavity. f 

It  was  noted  by  Saunders  that  after  ligature  of  the 
bile  duct  the  lymphatics  coming  from  the  liver  were 
filled  with  a  bilious  fluid  ;J  and  Richard  Powell  says 
that  in  one  case  of  jaundice  he  saw  evident  and  satis- 
factory marks  of  the  presence  of  bile  in  the  thoracic  duct.  § 
More  lately  an  important  contribution  to  the  investiga- 
tion of  the  manner  in  which  the  bile  leaves  the  liver  in 
jaundice  has  been  made  by  Fleischl.  Working  in  the 
Laboratory  at  Leipzig,  Ludwig  asked  him  to  notice  that, 
in  a  dog  whose  bile  duct  had  been  tied,  the  lymphatics 
from  the  porta  to  the  receptacuhtm  chyli  were  distended 
with  a  yellow  lymph  which  gave  Gmelin's  reaction.  Tak- 
ing up  the  matter  as  a  definite  research,  he  found  that  if 
the  bile  duct  were  tied,  and  a  cannula  inserted  into  the 
thoracic  duct  in  the  neck  of  a  large  dog,  that  the  lymph 
contained  abundance  of  bile  acids,  but  the  blood  not  a 
trace.     Hence  it  is  concluded  that  the  bile,  in   cases   of 

*  Heidenhain,  Studicn.  d.  phys.  Inst,  zii  Brcslau,  Leipzig,  1868,  Heft.  iv.  p.  233. 
f  P.  Picard,  Lyon  medical,  1879,  t.  xxxi.  p.  296. 

I  Saunders,  A    Treatise  on  the  Structure,  Economy,  and  Diseases  of  the  Liver, 
Lond.  1803,  Third  ed.  p.  112. 

§  Powell,  Observations  on  the  Bile  and  its  Diseases,  London,  1800,  p.  55. 


Histology  of  the  Liver  in  Jaundice.  351 

obstruction  of  the  gall-ducts,  passes  out  of  the  liver  by 
the  lymphatics  into  the  thoracic  duct,  and  thence  into 
the  blood.  If  both  the  common  bile  duct  and  the  tho- 
racic duct  be  tied  together,  no  bile  passes  into  the 
blood.* 

As  the  obstruction  lasts,  so  the  colour  of  the  liver 
becomes  deeper,  and  finally  of  a  dark  green,  the  cen- 
tral parts  of  the  acinus  retaining  the  deeper  tint,  even 
to  the  end  of  the  disease.  With  the  increased  depth  in 
colour,  the  liver  becomes  firmer  and  tougher,  and  in 
the  last  stages  of  all  shows  a  distinct  granular  appear- 
ance both  on  section  and  surface.  The  liver,  which  in 
the  early  stage  of  jaundice  showed  a  distinct  enlarge- 
ment, now  begins  to  shrink  ;  and  this  shrinking,  tough- 
ness, and  granular  look,  may  be  due  to  one  and  the 
same  cause,  an  increase  in  the  connective  tissue. 

The  histological  changes  of  the  liver  in  obstruction 
to  the  duct  had  been  until  lately  but  little  studied,* 
though  at  Paris  we  are  told  that  within  the  last  three 
years  the  subject  has  become  the  order  of  the  day. 
This  is  no  doubt  owing  to  the  experiments  of  Charcot 
on  this  point,  which  have  everywhere  drawn  much  at- 
tention. 

Oskar  Wyss  was  the  first  to  pay  much  attention  to 
this  state,  and  the  greater  part  of  his  research  was  de- 
voted to  describing  the  casts  of  the  inter-cellular  bile 
ducts,  which  may  be  seen  in  some  cases  of  jaundice,  but 
are  not  very  common.  He  describes  numerous  green 
or  greenish-brown  bodies,  of  a  rounded  or  lengthened 
shape,  sometimes  branched,  from  2   to   5   micro-milli- 

*  Fleischl,  Arheitcn  aiis  d.  phys.  Anstalt  zu  Leipzig,  1874.  Jahrg.  ix.  p.  24.  He 
has  noticed  that  many  lymphatics  leave  the  liver  with  the  connective  tissue  of  the 
hepatic  vein  as  well  as  by  the  porta. 

t  The  chief  writers  who  have  dealt  with  this  point  are:  Handfield  Jones,  Trans, 
of  the  Pathological  Society  of  London,  1854.  Vol.  v.  p.  146.  Frerichs,  op.  cit.  Bd.  i. 
pp.  122.  139.  and  248.  Bd.  ii.  p.  501.  Beale,  Archives  of  Medicine,  1859.  Vol.  i.  p. 
125.  Foerster,  Wiirzb.  med.  Zeitschrift,  1861.  Bd.  ii.  p.  161.  Klebs,  Handb.  d. 
path,  Anat.  Berlin,  1869.  Bd.  i.  p.  425. 


352  Histology  of  the  Liver  in  Jaimdice, 

meters  (xuoo  of  ^  millimeter)  in  diameter,  and  some- 
times reaching  13  micro-millimeters.  The  bodies  are 
only  found  between  the  liver  cells,  never  within  them, 
and  sometimes  form  a  complete  network  between  and 
about  the  cells.*  Oskar  Wyss  looks  upon  these  bodies 
as  casts  of  the  capillary  ducts,  varicose  from  distension 
with  bile,  an  opinion  in  which  most  will  be  inclined  to 
agree  with  him.  I  have  myself  verified  his  account  of 
these  bodies  on  several  occasions,  notably  in  a  case  of 
congenital  deficiency  of  the  ducts. f 

There  are  changes,  however,  which  the  cells  and  the 
capsule  of  Glisson  undergo,  and  which  it  will  be  con- 
venient to  describe  separately  from  one  another,  and 
also  to  consider  the  changes  in  the  capsule  of  Glisson 
before  the  changes  in  the  cells. 

There  may  be  found  some  signs  that  the  older  writers 
suspected  changes  in  the  connective  tissue  of  the  liver 
in  cases  of  obstruction  to  the  ducts.  Albers,  speaking 
of  these  cases,  describes  the  parenchyma  of  the  liver  as 
granular,  rough,  and  coloured  yellowish-brown  ;  while 
in  one  case,  he  says,  the  liver  was  really  cirrhotic  :  it 
appears  that  the  cellular  tissue  of  the  liver  is  partly 
atrophied,  partly  indurated. J  Andral  has  recorded  a 
case  which,  although  rendered  less  valuable  by  the  fact 
that  the  patient  was  a  drunkard,  yet  deserves  some 
attention.  The  bile  ducts  were  much  dilated,  and  the 
liver  was  small,  deep  green,  very  dense  and  granular 
on    the    surface    and    section, §       Yet    notwithstanding 

*  Oskar  Wyss,  Arch.f.patli.  Anat.  1866.  Bd.  xxxv.  p.  553. 

f  Wickham  Legg,  Trans,  of  the  Pathological  Society  of  London,  1876.  Vol.  xxvii. 
p.  181. 

J  Albers,  Beobachtnngcn  auf  dcm  Gcbicte  der  Pathologic,  Bonn,  1836.  p.  19. 

§  Andral,  Clinique  med.  Paris, .  1839.  46  ed.  t.  ii.  p.  534.  Virchow  (Wiirzb. 
Verhandl.  1857.  ^^'  ^ii.  p.  27.)  and  Liebermeister  {Bcitrdgc  zur  path.  Anat.  u. 
Klinik  d.  Leherkrankhcitcn,  Tubingen,  1864.  p.  135.)  both  seem  to  have  looked 
upon  the  irritation  caused  by  gall  stones  as  the  cause  of  the  increased  connective 
tissue  in  the  liver.  Cf.  a  case  by  Dr.  Henry  Green.  {Trans,  of  the  Path,  Soc. 
of  London,  1872.  Vol.  xxiii.  p.  133.) 


The  Overgrowth  of  the  Connective  Tissue.        353 

these  hints  as  to  the  granular  state  of  the  Hver,  Oskar 
Wyss  was  really  the  first  to  assert  an  over-growth  of 
the  connective  tissue,  and  yet  he  passes  it  by  in  a  few 
lines,  and  says  that  the  increase  is  never  very  great,  and 
that  no  increase  of  the  connective  tissue  within  the 
lobule  has  yet  been  seen.*  I  agree,  notwithstanding, 
with  Oskar  Wyss,  that  in  cases  of  slight  and  transient 
jaundice,  the  connective  tissue  of  the  liver  in  man  is 
not  increased.  It  is,  however,  far  otherwise  when  the 
jaundice  lasts  long  and  is  severe,  or  if  the  cause  of  the 
jaundice  be  one  which  would  beget  great  changes  in 
the  portal  canals.  Thus,  the  over-growth  of  the  con- 
nective tissue  is  very  great  in  animals  whose  bile  ducts 
have  been  tied.  The  increase  is  here  so  great  that  the 
liver  closely  resembles  that  of  a  drunkard ;  the  connec- 
tive tissue  is  studded  with  lymphatic  corpuscles  just 
as  in  cirrhosis,  and  the  new  connective  tissue  enters 
deeply  into  the  lobules. f  The  same  appearances  may 
be  met  with  in  man  when  the  obstruction  is  due  to  the 
presence  of  rough  angular  gall-stones  in  the  common 
duct,  but  especially  in  those  rare  cases  of  congenital 
deficiency  of  the  ducts.  A  less  overgrowth  of  the  con- 
nective tissue  may  be  met  with  in  cases  of  jaundice 
from  cancer  of  the  head  of  the  pancreas,  or  tumour 
pressing  upon  the  liver  from  the  outside.  The  very  least 
increase  of  the  connective  tissue  that  I  have  ever  met 
with   was    in    a    case    of  complete   obstruction   to   the 

*  Oskar  Wyss,  op.  cit.  p.  559. 

f  Heinrich  Mayer,  Strieker's  Mediz.  yahrhb.  hrsgeg.  von  d.  k.k.  Gesellschaft 
d.  Aerzte,  Wien,  1872.  p.  133.  Wickham  Legg,  St.  Bartholomew'' s  Hospital 
Reports,  1873.  Vol.  ix.  p.  161.  Charcot  and  Gombault,  Archives  de  Physiologie, 
1876.  p.  272.  Foa  and  Salvioli  {Archivi  per  le  Scienze  med.  1877.  quoted  in  Cen- 
tralblattf.  d.  med.  Wiss.  1878.  p.  600.)  have  repeated  this  experiment  on  many 
animals  of  different  tribes,  mammals  and  birds,  but  they  have  not  found  any  note- 
worthy changes  different  from  those  already  described. 

It  is  clear  that  it  is  only  by  means  of  animals  that  this  overgrowth  of  the  con- 
nective tissue  in  jaundice  could  be  demonstrated.  Any  similar  attempt  from  the 
liver  of  man  would  always  be  met  by  the  insinuation  that  the  patient  was  a  drunk- 
ard. 

AA 


354  ^^^^  Overgrowth  of  the  Connective  Tissue 

hepatic  duct  by  a  hydatid  tumour.  In  this  case  the  in- 
crease of  the  capsule  of  GUsson  was  so  shght  that  there 
was  a  complete  absence  of  the  lymphatic  corpuscles 
which  are  nearly  always  seen  in  cases  of  overgrowth 
of  the  connective  tissue  in  the  liver.  This  case  seems  to 
me  to  disprove  Charcot  and  Gombault's  theory,  that 
the  overgrowth  is  due  to  the  distension  of  the  ducts,* 
and  an  early  putrefaction  of  the  bile ;  for  here  the  dis- 
tension was  carried  to  the  utmost,  and  yet  no  cirrhosis 
arose. 

The  cause  of  this  overgrowth  of  the  capsule  of 
Glisson  is  obscure.  It  has  been  suggested  to  me  that 
it  may  be  due  to  the  ducts  feeling  (if  such  an  expres- 
sion be  allowed)  the  necessity  for  increased  resistance, 
and  thus  strengthening  themselves  by  adding  fibrous 
tissue  to  their  walls.  This  cannot  be,  however,  as  in 
the  case  just  mentioned  of  hydatid  tumour  completely 
obstructing  the  hepatic  duct,  there  was  abundance  of 
dilating  force  within  the  ducts,  and  yet  the  connective 
tissue  was  but  little  increased  in  comparison  with  other 
cases.  I  thought  at  one  time"|*  that  it  was  the  pres- 
ence of  the  ligature  in  the  portal  fissure  which,  in  the 
case  of  animals,  set  up  a  great  overgrowth  of  the  con- 
nective tissue  around  the  vessels,  which  extended  at  last 
to  the  liver.  In  connexion  with  this  view  it  is  inter- 
esting to  observe  that  a  like  overgrowth  of  the  connec- 
tive tissue  is  seen  when  the  portal  vein  has  been  tied 
after  Ore's  method. J  In  fact,  an  overgrowth  of  the 
connective  tissue  follows  many  other  disturbances  of 
the  circulation  in  the  liver,  as  in  nutmeg  liver. §  And 
in  the   kidney,  the  same  interstitial  process  is   set  up 

*  Charcot  and  Gombault,  op.  clt.  p.  289.  Dr.  Lionel  Beale  seems  in  some  degree  to 
favour,  by  anticipation,  Charcot's  theory  in  his  case  of  cirrhosis  from  obstruction. 
{Archives  of  Medicine,  1859.  Vol.  i.  p.  127.) 

f  Wickham  Legg,  op.  cit.  p.  178. 

X  Solowieff,  Arch.  f.  path.  Anat.  1875.  Bd.  Ixii.  p.  195. 

§  Wickham  Legg,  Med.  Chir.  Trans.  1875.  Vol.  Iviii.  p.  345. 


of  the  Liver  in  Jaundice.  355 

where  any  impediment  exists  to  the  flow  of  urine  out  of 
the  pelvis.  But  I  have  lately  met  with  a  case  which 
destroys  this  theory.  In  a  patient,  deeply  jaundiced,  I 
found  a  small  cancer,  not  larger  than  a  hazel  nut, 
placed  on  the  mucous  membrane  of  the  duodenum  and 
completely  obstructing  the  flow  of  bile  into  the  duo- 
denum. Here  there  was  no  interference  with  the  con- 
nective tissue  of  the  porta  ;  yet  the  liver  was  as 
markedly  cirrhotic  as  I  have  ever  seen  it  in  the  cir- 
rhosis from  obstruction  to  the  bile. 

Charcot  and  Gombault  have  found,  within  the  new 
connective  tissue  of  the  livers  of  animals  whose  bile 
ducts  had  been  tied,  a  developement  of  the  biliary  ducts 
like  that  described,  first  by  Waldeyer,*  and  afterwards 
by  Hanotjf  in  hypertrophous  cirrhosis.  The  account 
is  as  follows :  Under  the  microscope  is  seen  a  large 
number  of  winding  tubes,  often  anastomosing  and 
forming  a  network  with  irregular  meshes.  Their  num- 
ber, size,  and  general  direction,  vary  according  to  the 
point  looked  at ;  but  three  zones  could  sometimes  be 
distinguished  in  the  portal  space,  more  often  only  two  ; 
a  central  zone  filled  by  large  canals ;  these  are  not  very 
abundant,  and  fill  the  space  in  the  immediate  neigh- 
bourhood of  the  vein  ;  they  sometimes  are  prolonged 
into  the  fissure,  and  then  fill  the  middle  part ;  they  are 
in  general  separated  from  the  other  canals  by  a  broad 
zone  of  connective  tissue.  The  central  zone  is  the  most 
often  wanting.  There  is  also  a  middle  zone  in  which 
smaller  canals  are  found  than  in  the  first,  often  anasto- 
mosing, but  following,  as  a  rule,  a  direction  perpendi- 
cular to  those  of  the  vessels  which  radiate  from  the 
lobule  ;  lastly,  a  third  zone,  formed  by  very  short 
canals,  starting  at  a  right  angle  from  the  foregoing 
to  open  upon  the  lobule  in  a  direction  parallel  to  those 

*  Waldeyer,  Arch.f.  path.  Anat.  1868.  Bd.  xliii.  p.  537. 

f  Hanot,  Etude  sur  tine  forme  de  cirrhose  hypertrophiqtie  dufoic,  Paris,  1876. 

AA  2 


35^  Overgrowth  of  the  Connective  Tissue. 

rows  of  liver  cells  with  which  they  seem  in  certain 
places  to  be  continuous.  These  canals  are  the  least 
in  size  of  all.  The  contents  of  the  canals  are  variable. 
Sometimes  they  are  completely  filled  with  small  epithe- 
lium cells  ;  sometimes  they  form  on  the  inner  surface 
an  irregular  lining,  with  all  the  intermediate  stages 
between  the  cubical  epithelium  of  the  fine  interlobular 
canals  and  the  cylindrical  epithelium  of  the  larger 
ducts.  When  the  canal  possesses  a  free  cavity,  it 
is  sometimes  very  narrow,  sometimes  dilated.  In  the 
first  case  the  epithelium  is  large,  in  the  second  flat- 
tened. Lastly,  in  the  larger  canals,  the  cavity  may  be 
obstructed  by  a  mass  of  pigment. §  I  can  attest  that 
these  rudimentary  biliary  ducts  are  seen  in  cases  of 
obstruction  ;  for  I  have  recently  had  the  opportunity  of 
verifying  Charcot  and  Gombault's  statements  in  some 
cases  of  well-marked  cirrhosis  from  this  cause. 

It  is  clear  that,  if  the  increase  of  the  connective  tis- 
sue within  the  liver  be  at  all  great,  the  size  of  the  lobule 
must  decrease  ;  Charcot  and  Gombault  found  this  really 
was  the  case.  In  the  advanced  cases  the  shape  of  the 
lobule  was  much  changed,  and  in  a  curious  way.  The 
lobule  is  not  merely,  so  to  speak,  pushed  back  by  the 
developement  of  the  new  connective  tissue  ;  in  the  most 
wasted  of  all  the  lobules  the  hepatic  cells  kept  shape 
and  size,  and  even  their  regular  mode  of  arrangement. 
They  are  still  seen  in  rays  around  the  hepatic  vein,  but 
at  the  circumference  of  the  lobule  they  are  stopped 
abruptly,  and  each  ray  differs  in  length  so  that  the 
outline  of  the  lobules  becomes  very  irregular.  I  fear 
that  I  am  quite  unable  to  corroborate  the  statements  of 
Charcot  and  Gombault  in  this  particular.  In  my  own 
experiments  one  of  the  first  and  most  striking  results, 
was  the  destruction  of  the  natural  appearance  of  the 
cells  arranged  in  rays  around  the  vein.     The  cells  were 

*  Charcot  and  Gombault,  op.  cit.  1876.  p.  278. 


Changes' in  the  Liver  Cells.  357 

piled  irregularly  one  on  another  without  any  arrange- 
ment, and  the  atrophy  of  the  individual  cell  was  a 
marked  feature  in  the  later  cases. 

The  changes  which  take  place  in  the  cells  have  been 
studied  by  Oskar  Wyss,*  Henrich  Mayer,t  Leyden,J 
and  others.  Leyden  asserts,  basing  this  statement  on 
the  results  of  the  ligature  of  the  bile  ducts  in  more  than 
20  dogs,  that  the  cells  of  the  liver  undergo  a  fatty  infil- 
tration as  the  chief  change.  In  this  he  is  supported  by 
Hayem  and  Cornil.§  The  cells  in  the  centre  of  the 
acinus  were  quite  as  much  filled  with  fat  as  those  in 
the  circumference.  It  is  to  be  noted  that  the  bile  con- 
tained fat  drops,  and  the  epithelium  of  the  gall  bladder 
and  kidney  both  showed  a  fatty  infiltration.  Oskar 
Wyss,  Heinrich  Mayer  and  myself  did  not  find  any 
high  degree  of  fatty  infiltration  present.  In  my  own 
cases  I  found  a  certain  amount  of  fatty  infiltration  of 
the  outer  zone  of  the  lobule,  if  death  took  place  a  short 
time  after  the  obstruction  was  set  up  :  but  if  later,  very 
little  fat  was  present  in  the  cells  ;  and,  on  the  contrary, 
the  two  observers  mentioned,  and  myself,  found  a  wast- 
ing of  the  cells.  They  became  much  smaller  than  in 
health,  they  had  granular  contents  and  an  indistinct 
looking  nucleus,  which  Heinrich  Mayer  says  is  altered, 
without  more  specially  stating  the  nature  of  the  change. 
In  several  of  my  cases  I  have  been  unable  to  detect  a 
nucleus,  but  I  think  this  to  be  due  to  some  optical 
defect  rather  than  to  a  real  absence  of  the  nucleus. 
Charcot  and  Gombault  found  a  fatty  infiltration  quite 
the  exception.il 

They  are  unable  to  state  how  the  liver  cell  is  de- 

*  Oskar  Wyss,  loc.  cit. 
f  Heinrich  Mayer,  loc.  cit. 

X  Leyden,  Beitrdge  ziir  Pathologic  des  Icterus,  Berlin,  1866.  p.  83. 
§  Hayem  and  Cornil,  Comptes  rendus  des  Seances  de  la  Societe  de  Biologic, 
Annee  1875.  p.  309. 

II  Charcot  and  Gombault,  Archives  de  Physiologic,  1876.  p.  281. 


358  Changes  of  the  Liver  Cells. 

stroyed.  The  protoplasm  gradually  decreases,  the  cell 
lessens  in  size  and  becomes  angular  in  shape,  the  con- 
tents being  homogeneous,  shining,  and  slightly  yellow, 
like  glass.  The  protoplasm  does  not  colour  with  car- 
mine, but  the  nucleus  does.  Charcot  and  Gombault 
call  this  the  vitreous  degeneration.  I  have  seen  this 
appearance  in  my  experiments,  but  I  do  not  look  upon 
it  as  very  common. 

Chambard  has  repeated  the  experiments  of  Charcot 
and  Gombault  upon  guinea  pigs  and  has  come  to  re- 
sults closely  allied  to  theirs.*  He  has  paid  special  at- 
tention to  the  changes  undergone  by  the  cells,  and 
points  out  the  presence  of  many '' transparent  spots," 
as  he  calls  the  masses  of  cells  which  show  the  vitreous 
change  described  by  Charcot  and  Gombault.  Chambard 
discusses  the  question  if  these  transparent  spots  be  due 
to  the  bursting  of  a  bile  duct  and  the  action  of  the  bile 
upon  the  cells  in  the  neighbourhood;  but  rather  inclines 
to  the  belief  that  the  appearance  is  caused  by  the  filling 
of  the  cells  with  mucus. 

In  a  few  cases  of  permanent  obstruction  to  the  ducts 
the  liver  cells  have  been  completely  destroyed,  just  as 
in  acute  yellow  atrophy,  nothing  but  a  granular  and 
fatty  detritus  being  seen  under  the  microscope.  This 
appearance  is  very  rare,  and  has  gained  undue  pro- 
minence from  the  circumstance  that  in  the  very  first 
case  in  which  the  liver  cells  were  found  dissolved,  there 
was  a  complete  obstruction  to  the  ducts. +  To  explain 
this  solution  of  the  cells,  it  was  thought  by  Theodor 
von  Dusch  that  the  bile  had  the  property  of  dissolving 
the  liver  cells,  J  but  it  has  been  satisfactorily  disproved 

*  Ernest  Chambard,  Archives  de  Physiologic,  1877.  p.  718.  and  Laboratoire  d'His- 
tologie  dii  College  de  France,  travaux  de  Vannee  1877-78,  Paris,  1879,  p.  31. 

f  Thomas  Williams,  Guy^s  Hospital  Reports,  1843.  p.  444. 

\  Th.  von  Dusch,  Untersuchungcn  and  Expcriincnte  als  Beitrdg  zur  Patho- 
genese  des  Icterus,  Leipzig,  1854.  p.  36. 


The  Kidneys  in  Jaundice.  359 

by  Kiihne*  and  others,t  that  the  liver  cell  is  not'  dis- 
solved by  the  bile  acids,  but  that  its  outhne  merely  is 
rendered  indistinct  and  faint,  but  may  be  readily  re- 
stored by  adding  colouring  matter  to  the  shde.  Oskar 
Wyss  thinks  the  liver  cells  in  jaundice  are  more  easily 
destroyed  by  post-mortem  decomposition:  he  says  he 
has  been  unable  to  find  liver  cells  fi'om  a  case  of  jaun- 
dice 48  hours  after  death.;]:  This  cannot  be  gener- 
ally true,  as  I  have  kept  jaundiced  livers  even  in  hot 
weather  for  7  days,  and  yet  at  the  end  of  that  time  been 
able  to  recognise  the  cell.  Leyden  has  found  that  a 
parenchymatous  degeneration  of  the  liver  and  other 
glandular  and  muscular  organs  follows  the  poisoning 
by  bile  acids. §  It  would  be  well  to  keep  his  observa- 
tions in  mind  when  seeking  for  an  explanation  of  the 
dissolution  of  the  cells,  as  a  parenchymatous  degenera- 
tion may  end  in  a  complete  disappearance. 

Frerichs  has  very  fully  described  the  important 
changes  seen  in  the  kidneys.  No  one  before  him 
seems  to  have  paid  any  attention  to  their  histology  in 
jaundice.  As  the  greater  part  of  the  bile  pigment  leaves 
the  body  by  the  urine,  it  is  natural  to  expect  correspond- 
ing changes  in  the  kidneys.  After  a  long-continued 
jaundice,  Frerichs  finds  the  kidneys  of  an  olive  green 
tint ;  on  the  surface  are  seen  a  few  convoluted  tubes  of  a 
dark  colour  while  in  the  pyramids,  the  tubules  are  brown 
or  green  and  filled  with  black  deposit.  With  the  micro- 
scope, it  is  seen  that  the  paler  tubules  are  coloured  green 
or  brown.  The  epithelium,  rarely  completely  retained, 
is  coloured  deep  brown,  especially  the  nucleus.  The 
cells  themselves  appear  some  blood  red,  some  green, 
some  brown.     Others  show  layers  of  pigment  arranged 

*  Kiihne,  Arch.  f.  path.  Anat.  1858.  Vol.  xiv.  p.  334. 

f  Robin,  Memoires  Ins  a  la  Soc.  de  Biologic,  annee  1857.  P-  M'      See  also  my 
own  observations,  S.  B.  H.  Reports,  1873.  Vol.  ix.  p.  180. 
J  Oskar  Wyss,  loc.  cit. 
§  Leyden,  op.  cit.  p.  60. 


360  The  Kidneys  in  Jaundice. 

in  a  concentric  manner  around  the  nucleus.  Epithe- 
lium showing  marks  of  fatty  degeneration  may  often  be 
seen  of  a  red,  brown,  or  black  colour.  When  the  de- 
posit of  pigment  has  reached  its  highest  degree,  the 
tubules  appear  filled  with  a  coal  black,  firm  brittle 
mass.  This,  like  some  kinds  of  black  gall  stones, 
resists  the  action  of  caustic  potash  for  a  long  time. 
Sometimes  this  deposit  of  pigment  is  seen  everywhere 
throughout  the  kidney,  beginning  in  the  Mapighian 
bodies  where  it  is  less  marked,  and  passing  through  the 
convoluted  tubes  till  it  reaches  the  straight  tubules  of 
the  pyramid,  which  are  often  plugged  with  coal-black 
masses  of  pigment.* 

I  can  endorse  these  statements  of  Frerlchs ;  I  have 
seen  all  that  he  describes  and  have  very  little  to  add. 
In  some  cases  there  has  appeared  to  me  an  over- 
growth of  the  connective  tissue  of  the  kidney ;  but 
this  I  look  upon  as  an  accident,  as  in  a  child  which 
had  been  jaundiced  from  birth,  there  was  no  increase 
of  the  connective  tissue  of  the  kidney.  The  striation 
of  the  cortex  is  often  perfectly  retained  in  these  cases, 
and  the  kidney  simply  looks  jaundiced. 

Mobius  has  studied  the  state  of  the  kidney  in  jaun- 
dice, and  endeavours  to  supplement  Frerichs'  work  on 
this  subject.  If  a  moderate  amount  of  jaundice  have 
lasted  a  few  months,  the  kidneys  will  be  found  of  the 
natural  size  and  consistence,  and  the  surface  will  be 
smooth  and  yellow.  No  change  will  be  seen  in  the- re- 
lation between  the  pyramids  and  cortex :  this  last 
shows  a  diffuse  yellow  colour,  which  Mobius  compares 
to  mustard.  The  pyramids  show  dark  green  stripes, 
the  colour  of  which  is  most  intense  midway  between 
the  apex  and  base.  If  the  jaundice  have  lasted  but  a 
short  time  the  colour  is  much  less  marked  ;  while  if 
there    have   been    a    complete  obstruction    to   the  gall 

*  Frerichs,  op.  cit,  Bd.  i.  p.  107. 


Histology  of  other  Glands  and  the  Skin.  361 

ducts,  the  cortex  is  dark  yellow  ochre,  some  parts 
being  olive  green  and  the  green  lines  of  the  pyramids 
very  prominent,  becoming  in  some  places  black.  A 
scraping  of  the  organ  shows  under  the  microscope 
bright  yellow  granules  of  varying  size,  some  free, 
others  in  epitheUum  cells.  On  hardening  the  organ, 
the  following  appearances  can  be  made  out :  The  glo- 
meruli are  entirely  free  from  pigment  in  all  cases :  so 
also  is  the  interstitial  tissue ;  it  is  only  the  tubules 
which  show  pigment  granules,  and  these  are  contained 
in  the  epithelium  of  the  convoluted  tubes,  but  in  greater 
abundance  in  the  looped  tubes.  The  granules  are  most 
common  about  the  nucleus.  If  the  jaundice  last  long, 
the  inner  layer  of  the  capsule  is  coloured  golden  yellow, 
which  Mobius  thinks  is  due  to  the  filling  of  the  lympha- 
tic vessels  with  pigment.  The  epithelium  of  the  kidney 
becomes  more  and  more  filled  with  it,  and  the  tubules 
themselves  seem  filled  with  pigment,  so  as  to  form  casts 
of  tubes  formed  of  bile  pigment.  Mobius  found  no  pig- 
ment in  the  kidneys  in  a  case  of  phosphorus  poisoning, 
acute  yellow  atrophy,  or  pysemic  jaundice. f 

The  other  glands,  the  salivary  and  the  pancreas,  for 
example,  show  but  little  change.  Neither  do  the  sweat 
glands  offer  any  striking  morbid  appearance.  Frerichs 
says  that  now  and  then  the  contents  of  the  tubule  may 
appear  somewhat  yellow,  and  a  few  brown  pigment 
granules  be  seen,  but  nothing  more. J 

The  skin  as  a  rule  shows  after  death  no  change  in 
tint  from  that  in  life.  If  it  be  examined  with  the  micro- 
scope, it  is  found  to  show  in  the  lower  layers,  where  the 
epidermal  cells  are  youngest,  the  greatest  amount  of 
colour.  In  this  it  is  like  Addison's  disease.  The 
rounded  cells,  nearest  the  true  skin,  show  brown  and 
yellow  granules  about  the  nucleus. 

f  p.  J.  Mobius,  Arch,  d,  Heilkunde,  1877.  Jahrg.  xviii.  p.  83. 
X  Frerichs,  op.  cit.  Bd.  i.  p.  109. 


362  Mucous  Membranes  in  Jaundice. 

The  mucous  membranes  which  during  life  show  but 
little  of  the  yellow  tinge,  become  much  more  coloured 
after  death.  Care  'must  be  taken  in  all  cases  of  sus- 
pected jaundice  not  to  make  any  diagnosis  from  the 
colour  of  the  conjunctiva  after  death.  This  often  as- 
sumes a  distinctly  yellow  appearance,  even  where  no 
jaundice  or  symptom  of  liver  derangement  was  seen 
during  life. 


CHAPTER   XIV. 

The  Functions  of  the  Liver  in  Jaundice. 

But  little  attention  has  been  hitherto  paid  to  the  ques- 
tion whether  the  liver  continue  its  functions  in  jaundice 
as  in  health.  Indeed,  it  seems  by  some  to  have  been 
assumed  that  the  functions  go  on  without  interrup- 
tion. The  first  intimation,  since  Claude  Bernard's 
discoveries,  that  such  a  question  was  asked  may  be 
found  in  a  paper  by  Kiihne  on  jaundice.  Benzoic  acid, 
it  is  well  known,  is  converted  in  the  body  into  hippuric 
acid,  probably  by  combining  in  the  liver  with  glycocoll, 
in  the  presence  of  bile.*  Kiihne  asserts  that  if  benzoic 
acid  be  given  to  a  jaundiced  animal,  no  hippuric  acid 
is  seen  in  the  urine,  but  the  benzoic  acid  appears  un- 
altered. This  he  thinks  due  to  the  liver's  functions 
being  altered  in  jaundice,  so  that  no  more  free  gly- 
cocoll or  glycocholic  acid  is  formed  in  the  liver,  but 
only  taurocholic  or  cholalic  acid.f  Kiihne's  theory, 
however,  was  quickly  made  an  end  of;  for  several 
observers  found  that  the  disappearance  of  the  hippuric 
acid  was  due  rather  to  the  decomposition  of  urine,  and 
the  reappearance  of  benzoic  acid  from  putrefaction  than 
to  any  other  cause. J 

Golowin  was  the  next,  at  the  suggestion  of  Botkin, 
to  raise  any  doubts  as  to  the  functions  of  the  liver. 
From  observations  on  jaundiced  men  and  dogs,  he 
came  to  the  conclusion  that  the  liver  at  the  end  of  a 
long-continued  jaundice  lost  the  power  of  secreting  bile 
acids. §     His  observations  will  be  spoken  of  again. 

*  Kiihne  and  Hallwachs,  Arch.f.  path.  Anat.  1857,  Bd.  xii.  p.  386. 
f  Kiihne,  ibid.  1858,  Bd.  xiv.  p.  320. 

I  See  p.  293  of  this  work. 

*  Golowin,  Arch.  f.  path.  Anat.  1871,  Bd,  liii.  p.  417. 


364  ■  In  Jaundice  the  Liver 

'  Skoda  looks  upon  the  view  that  the  bile  continues  to 
be  secreted  in  continued  obstruction  as  venturesome, 
and  that  it  is  more  probable  that  the  pressure  in  the 
ducts  causes  a  hindrance  to  the  secretion  .of  the  cells. 
He  even  goes  so  far  as  to  think  that  jaundice  may  be 
absent  in  complete  obstruction  to  the  ducts.  Jaundice 
may  decrease  even  if  no  bile  pass  into  the  intestine.* 
Very  similar  views  are  expressed  by  Jaccoud.f 

The  disturbing  influence  of  jaundice  upon  the  several 
functions  of  the  liver  will  now  be  considered,  each 
function  being  taken  by  itself. 

i.  The  most  important  function  of  the  liver  known 
to  us  at  the  present  day  is  the  preparation  of  glyco- 
gen. This  appeared  to  me  so  important  a  point  to 
establish  on  a  firm  basis,  that  I  have  made  a  large 
number  of  observations  upon  animals  in  order  to  decide 
this  point.  In  all  cases  I  found  that  whether  the  ani- 
mal died  within  a  few  hours  or  a  few  days  after  ligature 
of  the  bile  ducts,  in  all  cases  alike,  glycogen  was  absent 
from  the  liver.  Glycogen  was  absent  in  all  cases  ;  it  is 
not,  therefore,  merely  the  outcome  of  temporary  distur- 
bance due  to  the  changes  set  up  by  the  wound  and  other 
circumstances,  but  a  permanent  change  in  the  function 
of  the  liver.  The  glycogen  in  no  case  returned  again.  J 
These  observations  have  been  confirmed  by  von  Wittich,§ 
E.  Kiilz,  and  E.  Frerichs.||  In  like  manner,  puncture 
of  the  fourth  ventricle  failed  to  cause  sugar  to  be  present 
in  the  urine  a  few  days  after  ligature  of  the  common 
duct.^I  It  is  evident,  therefore,  that  in  complete  ob- 
struction of  the  ducts  the  liver  ceases  to  prepare  gly- 
cogen. 

*  Skoda,  Virchow  and  Hirsch's  jfahresheyicht  f.  1868,  Bd.  ii.  p.  142. 

f  Jaccoud,  Lcrons  de  cliniquc  mid.  (Lariboisicre),  Paris,  1873,  p.  545. 

X  Wickham  Legg,  S.  Bartholomew's  Hospital  Reports,  1873,  Vol.  ix.  p.  161. 

§  Von  Wittich,  Centralblatt  f.  d.  med.  Wiss.  1875.  p.  291. 

II  E.  Kiilz  and  E.  Frerichs,  Arch,  f.  d.  ges.  Phys.  iZ'jQ.  Bd.  xiii.  p.  460. 

U  Wickham  Legg,  Arch.  f.  exp.  Path.  1874.  Bd.  ii.  p.  384. 


ceases  to  prepare  Glycogen.  365 

It  becomes  a  question  now  how  far  this  fact  in  animals 
may  be  apphed  to  jaundice  in  men,  when  there  is  some- 
times evidence,  from  the  presence  of  colour  in  the  stools, 
that  the  obstruction  to  the  ducts  is  not  complete.  In 
these  and  other  cases,  the  phsenomena  seem  best  ex- 
plained by  supposing  that  the  glycogenetic  function  of 
the  liver  is  not  altogether  abolished,  but  rather  impaired. 
Even  in  cases  of  simple  jaundice  the  patient  wastes  and 
loses  flesh  rapidly,  and  this  seems  best  explained  by 
supposing  a  great  impairment,  if  not  destruction,  of 
the  glycogenetic  function.  Glycogen  is  always  found 
in  growing  parts,  and  its  importance  to  nutrition  cannot 
be  doubted. 

The  like  absence  of  glycogen  and  sugar  in  the  liver 
was  found  by  Kiithe  in  dogs  in  whom  a  biliary  fistula 
had  been  established.  The  wasting  which  follows  the 
setting-up  of  this  flux  is  well-known.* 

There  is  a  case  of  Dr.  Bright's,  often  quoted,  of  the 
concurrence  of  jaundice  and  diabetes.  It  is  highly  in- 
teresting. A  man  aged  49,  of  sober  habits,  became 
diabetic  in  March,  1827.  At  the  beginning  of  Septem- 
ber he  became  jaundiced,  and  by  the  end  of  December, 
the  diabetes  had  disappeared.  He  died  on  March  ist, 
and  the  cause  of  death  was  found  in  a  tumour  of  the 
pancreas,  in  which  the  dilated  bile  ducts  terminated  in 
a  cul  de  sac^  Here  the  diabetes  continued  until  it  was 
put  an  end  to  by  a  permanent  obstruction  of  the  bile 
ducts. 

ii.  There  is  a  second  function  of  the  liver,  the  secre- 
tion of  bile.  Now  the  important  constituents  of  the  bile 
are  the  pigment,  the  bile  acids,  and  cholestearin.  The 
amount  of  bile  excreted  by  a  healthy  man  has  been  very 
variously  estimated.  Let  us  take  10  grammes,  the  esti- 
mation of  Westphalen,J  so  that  the  following  figures 

*  Kiithe,  Ztir  Function  der  Leber,  in  Heynsius'  Stud.  d.  phys.  Inst,  zu  Amster- 
dam, Leipzig  and  Heidelberg,  1861.  p.  52. 

f  Bright,  Med.  Chir.  Trans.  1833.  Vol.  xviii.  p.  3. 
%  See  p.  105  of  this  work. 


366  Amount  of  Bile  formed 

may  be  within  the  bounds  of  probability.  Of  these  10 
grammes  of  dry  bile,  5  must  be  made  up  of  the  soda 
salts  of  the  bile  acids,  about  one  by  mucus  and  pigment, 
and  the  remainder  by  cholestearin  and  the  inorganic 
residues.  Now  if  the  liver  in  jaundice  continue  its 
functions  of  bile-making  uninjured,  there  ought  to  pass 
out  of  the  system  daily,  amounts  of  bile-  pigment  and 
bile  acids  equivalent  to  these.  The  only  secretion 
which  has  been  hitherto  found  to  contain  them  is  the 
urine  ;  and  the  urine  therefore  is  to  be  examined  with 
this  view. 

First  as  to  the  bile  pigments.  The  urine  is  often 
deeply  coloured,  and  its  appearance  would  almost  justify 
the  belief  that  the  same  amount  of  the  bile  pigments 
which  in  health  is  passed  into  the  duodenum  must  be  con- 
tained in  the  urine.  Yet  Schwanda  in  his  estimations 
found  surprisingly  little  pigment.  In  the  highest,  the 
amount  was  only  '015  grm.  in  the  twenty-four  hours. 
In  others,  '014,  '012,  'Oii,  "005,  and  even  -002,  that  is', 
only  2  milligrammes.*  Thus  the  amount  of  pigment 
excreted  by  the  urine  is  infinitely  little  when  compared 
to  the  amount  of  pigment  excreted  by  the  liver  in  health. 
What  is  the  reason  of  this  difference  ?  To  me  the  best 
answer  to  this  question  seems  to  be  that  in  jaundice 
the  pigment-forming  function  of  the  liver  is  much  in- 
jured. I  am  aware  of  the  difficulties  which  this  solution 
itself  raises,  but  at  present  this  theory  seems  to  me  best 
to  explain  facts. 

Then  as  to  the  bile  acids.  The  part  which  these 
play  in  the  phsenomena  of  jaundice  has  for  some  years 
past  been  a  crux  to  pathologists.  Formerly  they  could 
not  be  found  in  the  urine,  and  there  was  great  strife  as 
to  the  cause  of  their  absence.      Now  all  agree  that  the 

*  Schwanda,  Wicn.  mcd.  Wochcnschrift,  1865.  p.  g8g.  See  above,  p.  30.  for  the 
observations  of  Stadeler  on  the  great  colouring  powers  of  the  bile  pigment.  A 
solution  of  one  in  a  million  was  distinctly  yellow  in  a  two-inch  la5'er. 


by  the  Liver  in  Jaundice.  367 

bile  acids  are  present  in  the  urine ;  but  they  are  present 
in  very  small  quantity.  At  the  reckoning  given  above 
the  liver  ought  daily  to  secrete  at  least  five  grammes  of 
the  bile  acids.  Now  in  jaundice,  if  we  may  believe 
what  the  chemists  tell  us,  not  so  much  as  half  a  gramme 
passes  out  of  the  body  daily  by  the  urine.  If  the  whole 
of  the  natural  amount  of  the  bile  acids  be  secreted, 
what  becomes  of  the  remaining  four  and  a  half  grammes  ? 
Ernst  Bischoff,  in  answer  to  this  question,  imagines  that 
the  blood  has  the  power  of  burning  off  so  much  of  the 
bile  acids,  and  no  more  ;  that  in  jaundice  more  bile 
acids  are  taken  into  the  blood  than  can  be  destroyed 
there,  and  that  then  the  unconsumed  excess  is  excreted 
by  the  kidneys.*  He  thinks  there  are  only  two  hypo- 
theses ;  one,  that  the  bile  acids  cannot  be  destroyed  in 
the  blood,  and  so  do  not  pass  into  it  in  health ;  or  that 
in  jaundice  more  bile  passes  into  the  blood  than  can 
be  consumed  therein.  He  hardly  contemplates  the 
possibility  of  the  bile  acids  ceasing  to  be  secreted  in 
jaundice ;  in  fact  he  brings  forward  some  reasoning 
and  experiments  which  seem  to  show  that  all  the  sul- 
phur of  the  bile  acids  which  should  be  excreted  per  anum^ 
passes  out  in  jaundice  through  the  urine. f 

Leyden  criticises  Ernst  Bischoff's  theory  by  noting 
that  even  in  slight  cases  of  jaundice  the  bile  acids  may 
be  found  in  the  urine.  If  any  quantity  of  the  bile  acids 
were  burnt  off  in  the  blood,  there  would  in  such  cases 
be  no  excess  to  appear  in  the  urine.     Also  if  bile  acids 

*  Ernst  Bischoff,  Zcitschrift  f.  rat.  Med.  1864.  iii.  Reihe,  Bd.  xxi.  p.  144. 

f  He  reasons  thus :  dry  bile  contains  from  '83  to  2-99  per  cent,  of  sulphur :  the 
mean  is  i'5  per  cent.  Now  taking  17  grm.  as  the  amount  of  dry  bile  daily  passing 
down  the  common  duct  (a  low  estimation)  -3  grm.  of  sulphur  are  daily  excreted. 
But  the  faeces  do  not  contain  all  this  sulphur,  part  is  absorbed  and  probably  passes 
out  in  the  urine  :  the  amount  of  sulphur  passed  in  health  by  stool  is  only  -26  grm. 
Now  in  jaundice  there  is  exactly  '26  grm.  of  sulphur  in  the  urine  more  than  in 
health.  Bischoff  seems  to  suggest  that  the  taurocholic  acid  is  the  source  of  this 
extra  sulphur,  [op.  cit.  p.  147.)  This  reasoning  is  open  to  many  objections.  It  has 
been  criticized  by  Leyden.     {op.  cit  p.  37.) 


368  Amount  of  Bile  formed 

be  injected  under  the  skin  of  rabbits,  they  make  their 
appearance  in  the  urine,  and  the  absorption  is  certainly 
very  slow.  And  in  these  cases  and  in  jaundice  it  is  a 
long  time  before  the  bile  acids  entirely  disappear  from 
the  urine.  But  it  is  very  important  that  the  resistance 
of  the  bile  acids  to  chemical  action  should  be  borne 
in  mind.  They  do  not  readily  decompose  even  when 
added  to  putrid  urine.* 

There  is,  moreover,  an  objection  at  first  sight  to  be- 
lieving that  the  secretion  of  bile  is  unaltered  in  jaun- 
dice :  it  seems  hardly  likely  that  when  the  excretory 
duct  of  a  gland  is  obstructed,  the  secretion  into  that 
duct  should  continue  unchecked.  Again  Schiff  thinks 
that  a  kind  of  circulation  of  bile  between  the  liver  and 
intestine  goes  on,  and  that  when  the  supply  of  bile  is 
cut  off  from  the  intestine,  the  amount  of  bile  becomes 
much  less.f  Further,  H.  Huppert  found  that  when 
the  bile  acids  are  injected  into  the  blood,  a  considerable 
excess  of  bile  acids  is  excreted  by  the  liver  in  the  bile.  J 
It  is  thus  possible  that  in  jaundice  the  secretion  of  bile 
acids  is  much  lessened,  as  no  supply  is  drawn  from  the 
intestines,  the  gall  duct  being  blocked  up.  Looking 
therefore  at  these  facts  just  mentioned,  the  undoubted 
smallness  of  the  amount  of  bile  acids  in  the  urine  of 
jaundice  and  the  intimate  connexion  between  the  bile- 
making  function  and  the  glycogenetic  function, §  it 
would  seem  the  most  probable  theory  that  in  jaundice 
very  little  of  the  bile  acids  is  secreted ;  and  that,  when 

*  Leyden,  Beitrdge  zur  Pathologic  des  Icterus,  Berlin,  1866.  p.  40. 

f  Schiff,  Arch.  f.  d.  gcs.  Phys.  1870.  Bd.  iii.  p.  598. 

X  H.  Huppert,  Arch.  d.  Heilkimde,  1864,  p.  244. 

§  That  there  is  an  intimate  connexion  between  the  two  can  scarcely  be 
doubted.  Bernard  found  in  the  Liniax  that  the  liver  alternately  secreted  bile  and 
sugar.  (Lemons  snr  Ics  proprictcs  physiologiqucs  ct  Ics  alterations  pathologiqucs  dcs 
liquides  de  Vorganisme,  Paris.  1859.  t.  ii.  p.  203.)  It  is  probable  also  that  albu- 
minous matters  are  broken  up  in  the  liver,  the  carbon,  hydrogen,  and  oxygen, 
going  to  form  glycogen,  while  the  refuse  of  this  process,  the  carbon,  hydrogen, 
oxygen,  sulphur  and  nitrogen,  forms  the  bile  acids. 


by  the  Liver  in  Jaundice.  369 

the  jaundice  is  of  long  standing,  and  the  glycogenetic 
function  completely  abolished,  the  bile  acids  likewise 
cease  to  be  secreted,  as  the  observations  of  Golowin 
and  others  teach.* 

What  is  now  wanted  are  more  and  accurate  estima- 
tions of  the  amount  of  bile  acids  passed  in  the  urine  of 
jaundice.  Some  may  doubt  if  the  amount  of  bile  acids 
have  ever  been  accurately  estimated  ;  but  there  is  no 
good  reason  for  denying  that  the  amount  is  very  small ; 
and  the  quantity  given  above,  half  a  gramme,  is  far 
higher  than  that  given  by  any  observer  who  has  esti- 
mated them. 

It  may  well  be  asked  :  why,  if  the  secretion  of  bile 
be  entirely  stopped,  do  the  skin  and  urine  become  so 
coloured  ?  To  this  it  may  be  answered  :  it  is  not  af- 
firmed that  the  secretion  of  bile  is  entirely  suppressed  ; 
witness  the  presence  of  the  bile  acids  and  bile  pigment 
in  the  urine,  though  in  small  quantity  ;  and  if  a  small 
quantity  of  bile  pigment  only  be  secreted,  it  would  be 
enough  to  colour  the  skin  and  urine.  The  yellow 
colour  which  is  common  in  jaundice  is  indeed  an  argu- 
ment in  favour  of  the  secretion  being  suppressed  ;  for 
•if  the  whole  amount  of  pigment,  natural  in  health,  con- 
tinued to  be  secreted,  the  skin  of  every  jaundiced  Euro- 
pean would  resemble  a  negro.  That  there  is  a  decrease 
of  the  amount  of  pigment  is  attested  by  Dr.  Budd  who 
says:  "It  sometimes  happens  that  after  complete 
closure  of  the  common  duct  has  existed  many  months, 
and  while  no  bile  flows  through  it  into  the  intestine,  the 
jaundice  of  the  skin  becomes  very  much  less  deep,  and 
the  urine  very  much  less  deeply  stained  with  bile.  I 
have,  indeed,  more  than  once  known  the  jaundice  gra- 
dually diminish  and  almost  entirely  disappear  after  the 
lapse  of  twelve  months,  to  the  great  satisfaction  of  the 
patient,  although  the  colour  of  the  intestinal  discharges 

*  See  the  section  on  the  urine,  p.  2S6  of  this  work. 

BB 


370  Lowered  Temperature  of  the  Body 

and  an  examination  of  the  body  after  death,  showed 
that  the  closure  of  the  duct  was  still  complete."*  Dr. 
Murchison  has  some  remarks  to  the  same  effect,  j" 

iii.  A  third  important  function  of  the  liver  is  the 
maintenance  of  animal  heat.  For  the  discovery  of  this 
important  office  we  are  again  indebted  to  Claude 
Bernard.  He  found  that  the  temperature  of  the  blood 
coming  from  the  hepatic  veins  was  higher  than  that  of 
any  other  part  of  the  body.J  The  high  temperature  is 
clearly  due  to  the  active  chemical  processes  which  go 
on  in  the  liver,  the  oxydations  connected  with  the  for- 
mation of  glycogen,  of  bile,  and  with  the  process  of 
sanguification.  If  the  arguments  used  in  the  foregoing 
paragraphs  be  at  all  sound,  it  should  follow  that,  in  ob- 
struction to  the  ducts  of  the  liver,  and  consequent  abo- 
lition of  two  important  functions,  the  temperature  of 
this  organ  should  fall,  and  with  it  the  temperature  of 
the  whole  of  the  body.  It  is  notorious  that  the  tem- 
perature in  jaundice  is  almost  always  below  the  natural 
standard ;  and  that  even  in  those  cases  where  a  pyrexial 
complication  is  present,  the  temperature  never  rises  so 
high  as  is  customary  in  uncomplicated  disorders. 

While  passing  through  Lyons  after  the  Easter  of 
1878  I  had  an  opportunity,  thanks  to  the  courtesy  of 
M.  Chauveau,  of  making  some  experiments  directed  to 
this  point.  The  bile  ducts  of  dogs  were  ligatured,  and 
forty-eight  hours  after  the  ligature  of  the  ducts,  the 
temperature  in  the  upper  part  of  the  inferior  cava  was 
ascertained,  by  means  of  a  thermometer  passed  through 
the  jugular  and  right  auricle.  It  was  found,  however, 
that  a  traumatic  pyrexia  had  been  set  up,  and  the  tem- 
perature of  the  vena  cava  and  of  the  rectum  was  in  all 


*  Budd,  On  Diseases  of  the  Liver,  London,  1857.  p.  231. 

f  Murchison,  Clinical  Lectures  on  Diseases  of  tlic  Liver,  London,  1868.  p.  427. 
X  Bernard,  Lemons  siir  les  proprietes physiologiqucs  ct  Ics  alterations  pathologiques 
des  Uqnides  de  I'organisvie,  Paris,  1859.  ^-  '•  P-  ^5- 


and  Sanguification  in  Jaundice.  371 

cases  equal.  It  would  be  necessary,  in  any  other  series 
of  experiments,  to  wait  until  the  pyrexia  had  gone  down. 
This,  again,  involves  a  risk,  as  the  animals  are  not 
likely  to  survive  the  operation  many  days. 

iv.  There  is  said  to  be  another  function  of  the  liver, 
to  which  allusion  has  already  been  made  ;  that  of  san- 
guification. C.  G.  Lehmann  found  the  blood  of  the 
hepatic  vein  to  contain  a  far  greater  number  of  red  and 
colourless  corpuscles  than  that  of  the  portal  vein.  The 
number  of  the  colourless  corpuscles  is  also  increased 
relatively  to  the  red.  The  red  are  distinctly  violet  in 
colour,  and  they  resist  the  action  of  water  upon  them.* 
He  also  says  that  the  red  corpuscles  are  smaller,  and 
less  regularly  lenticular.f  The  blood  of  the  portal  vein 
also  shows  fibrin  in  no  way  different  from  that  of  the 
rest  of  the  body  :  but  the  blood  from  the  hepatic  vein  can 
hardly  be  got  to  clot  at  all,  and  when  whipped,  shows 
only  a  few  threads  of  fibrin.  The  extractives  and  fats 
are  also  in  greater  quantity  in  the  hepatic  vein  than  in 
the  portal. J 

Ernst  Hirt  confirms  Lehmann's  statement  as  to  the 
increase  of  the  white  corpuscles  ;  he  finds  that  the 
number  of  white  corpuscles  to  the  red  in  the  blood 
of  the  portal  vein  is  about  i  to  700  or  750,  while  in 
the  hepatic  vein  the  number  is  about  i  in  68  or  274.  § 

Dr.  McDonnell,  so  well  known  from  the  numerous 
observations  which  he  has  made  on  the  functions  of  the 
liver,  affirms  without  hesitation  that  the  blood  of  the 
hepatic  veins  of  dogs  is  not  capable  of  coagulating 
spontaneously,  and  that  it  does  not  give  fibrin  on  being 
whipped,  and  that  the  hepatic  blood  contains  colour- 

*  C.  G.  Lehmann,  Physiological  Chemistry,  Cavendish  Soc.  ed.  Vol.  ii.  p.  259. 

f  Idem,  yournal  de  Pharniacic  ct  dc  Chiinic,  1852.  t.  xxi.  p.  396. 

];  Idem,  Comptcs  ycndus,  1855.  t.  xl.  p.  585.  The  absence  of  coagulation  in  the 
blood  of  the  hepatic  vein  has  also  been  noted  by  Brown-Sequard.  [journal  de  la 
Physiologie,  185S.  t.  i.  p.  298.) 

§  Ernst  Hirt,  Miiller's  Archiv.f.  Anat.  Phys.  1856.  p.  igi. 

BB2 


372  Lessened  Sangtiification  in  Jaundice. 

less  corpuscles  five  to  ten  times  more  numerous  than  in 
the  portal  blood.* 

Fliigge,  comparing  analyses  of  the  blood  of  the  portal 
and  hepatic  vein,  has  come  to  the  conclusion  that  there 
is  but  little  difference  between  the  blood  in  these  two 
vessels.  He  found  the  amount  of  the  solids,  nitrogen, 
phosphates,  and  chlorides,  almost  the  same  in  both, 
and  the  amount  of  haemoglobin  about  equal.  So  that 
if  Fliigge's  observations  and  his  method  may  be  trusted, 
great  doubts  will  be  thrown  upon  the  functions  of  the 
liver  as  a  blood-making  organ. f 

Drosdoff,  however,  has  made  analyses  of  the  blood  of 
the  portal  and  hepatic  veins  in  Hoppe-Seyler's  laboratory 
in  Strassburg,  and  sharply  criticises  Fliigge's  methods. 
Drosdoff  finds  that  the  solids  of  the  portal  vein  are 
always  greater  than  those  of  the  hepatic,  and  that  the 
hepatic  vein  is  always  richer  in  cholestearin  and  lecithin 
than  the  portal  vein,  while  the  reverse  holds  good  about 
fats4 

There  are  many  analyses  and  observations  which 
show  that  in  jaundice  the  amount  of  red  corpuscles 
is  much  decreased. §  Budd  attributes  this  not  so  much 
to  the  mere  presence  of  the  principles  of  the  bile  in  the 
blood,  as  to  the  diminution  of  those  reparative  changes 
which  the  blood  naturally  undergoes  in  its  passage 
through  the  liver,  and  on  the  absence  of  bile  in  the 
intestines. II  I  feel  disposed  to  agree  with  Budd  rather 
than  with  Leyden,  who  thinks  that  the  poorness  of  the 
blood  is  due  to  the  action  of  the  bile  acids  upon  the 
blood  corpuscles.^     For  if,   as  in  the  foregoing  para- 


*  McDonnell,  Ohscrvatiuus  on  the  functions  of  the  Liver,  Dublin,  1S65.  pp.   28 
and  38. 

f  Fliigge,  Zcitschrift f.  Biologic,  1877.  Bd.  xiii.  p.  133. 

+  W.  Drosdoff,  Zcitschrift  f.  phys.  Chcmic,  1877.  Bd.  i.  p.  233. 

§  See  the  section  on  the  blood  in  jaundice,  p.  269. 

II  Budd,  On  Diseases  of  the  Liver,  London,  1857.  Third  Edition,  p.  468. 

II  Leyden,  Bcitragc  zur  Pathologic  dcs  Icterus,  Berlin,  1S66.  p.  118. 


Lessened  Sanguification  in  Jaundice.  373 

graph  upon  the  secretion  of  the  bile  I  have  endeavoured 
to  show,  the  whole  amount  of  bile  acids  poured  into  the 
circulation  daily  be  less  than  half  a  gramme,  the  action 
of  the  bile  acids  upon  the  corpuscles  must  be  extremely 
small,  since  the  bile  acids  will  be  in  so  dilute  a  solution 
that  they  can  scarcely  be  thought  to  act  on  the  cor- 
puscles. 


CHAPTER   XV. 

The  Diagnosis  and  Prognosis  of  Jaundice. 

Diagnosis.  The  diagnosis  of  jaundice  is  commonly  a 
matter  of  extreme  ease.  All  that  is  necessary  is  to  look 
at  the  patient's  face,  and  especially  the  conjunctiva,  by 
daylight.  To  confirm  this  observation  it  is  often  desir- 
able to  ascertain  the  presence  of  bile  pigment  in  the 
urine,  and  the  absence  of  colour  in  the  faeces. 

There  is  one  discoloration  of  the  face  very  liable  at 
a  superficial  glance  to  be  mistaken  for  jaundice,  and 
that  is  the  yellowness  caused  by  exposure  to  the  sun. 
It  is  seen,  of  course,  chiefly  in  men,  but  the  conjunctivae 
remain  colourless,  and  the  urine  free  from  bile  pigment. 
Further,  the  parts  covered  by  clothing  are  of  the  natural 
white. 

The  same  pearly  whiteness  of  the  conjunctiva,  and 
absence  of  the  bile  pigment  from  the  urine  distinguish 
chlorosis,  in  which  the  skin  is  often  of  a  yellowish  tinge, 
the  cachexia  of  cancer,  lead  poisoning,  and  agues.  It 
seems  unlikely  that  the  pigmentation  of  the  skin  in 
Addison's  disease  should  be  mistaken  for  jaundice;  and 
some  assert  that  the  yellowness  of  the  new-born  is  shown 
not  to  be  a  jaundice  by  the  absence  of  colour  from  the 
conjunctivas  and  of  bile  pigment  from  the  urine. 

In  some  persons  a  layer  of  fat  lies  immediately  under 
the  conjunctiva,  and  it  is  necessar)^  to  add  a  caution  to 
the  young  practitioner,  not  to  be  deceived  by  this,  as  it 
causes  a  yellow  appearance  liable  to  be  mistaken  for 
slight  jaundice.  It  will  be  known  because  the  yellow 
colour  is  not  present  everywhere  in  the  conjunctiva, 
but  only  in  those  parts  of  the  sclerotic  where  the  fat  is 
most  abundant. 


Diagnosis  of  Jaundice.  375 

Jaundice  may  be  feigned  by  soldiers,  sailors,  and 
prisoners,  for  their  own  purposes.  It  is  done  by  stain- 
ing the  skin  with  any  yellow  pigment :  infusions  of 
saffron,  turmeric,  and  the  like  are  said  to  be  those 
most  commonly  employed.  Such  deception  may  be 
easily  detected,  as  the  conjunctivae  remained  unco- 
loured  ;  and  a  little  soap  and  water,  or  chlorine  water, 
or  chloride  of  lime,  will  discharge  the  colour  of  the 
skin.  If  their  cunning  have  gone  the  length  of  taking 
rhubarb  or  santonin  for  the  purpose  of  darkening  the 
urine,  the  urine  will  be  deepened  to  a  red  by  alkalies, 
whereas  the  urine  of  true  jaundice  is  coloured  brown. 
Further,  there  will  be  no  reaction  with  nitric  acid. 

A  far  better  means  for  deceiving  the  physician  would 
be  the  carbazotate  or  picrate  of  potash  taken  internally. 
This  is  said  to  stain  the  skin  and  tissues  of  a  fine 
yellow,  but  the  urine  does  not  contain  bile  pigment, 
nor  are  the  stools  colourless. 

Nothing  can  be  easier  than  to  say  that  a  patient  is 
jaundiced ;  but  it  is  often  one  of  the  most  difficult 
problems  in  medicine  to  point  out  the  cause  of  the 
jaundice.  It  is  sometimes  hard  even  to  approach  a 
diagnosis,  nothing  but  a  guess  being  possible ;  and  it 
is  not  often  that  the  physician  can  feel  very  great  con- 
fidence in  the  opinion  which  he  puts  forth.  A  few 
suggestions  are  added  upon  the  lines  of  which  the 
clinical  physician  may  work  in  his  search  after  the 
causes  of  jaundice. 

First,  it  is  of  considerable  importance  to  be  able  to 
feel  the  distended  gall-bladder  at  the  lower  border  of 
the  right  lobe.  If  this  can  be  distinctly  felt  and  per- 
cussed out,  much  information  is  gained.  The  cause  of 
•the  jaundice  will  in  all  likelihood  be  below  the  junction 
of  the  cystic  and  hepatic  ducts,  in  fact,  in  the  common 
duct.  In  cases  where  the  jaundice  is  due  to  changes 
in  the  liver  itself  the  gall-bladder  is  very  often  empty 
or  only  half  filled,  and  cannot  therefore  be  felt. 


376  Diagnosis  of  jaundice. 

Next,  the  state  of  the  stools  must  be  looked  into, 
whether  they  be  altogether  or  but  partly  free  from 
colour.  It  may  be  thought  by  some  that  a  complete 
absence  of  colour  in  the  stools  is  a  sign  of  complete 
obstruction  of  the  duct. 

i.  Should  the  jaundice  be  recent  and  no  perceptible 
disease  be  found  in  the  liver  or  elsewhere,  the  case  is 
probably  one  of  simple  jaundice. 

ii.  The  jaundice  being  recent  but  acute  disease  of 
other  parts  present :  such  as  pneumonia,  pyaemia, 
typhoid  and  relapsing  fevers,  and  the  like,  delirium 
tremens,  poisoning  by  chloroform,  chloral  hydrate 
and  other  drugs,  and  snake-bites,  the  cause  of  the 
jaundice  is  not  known  with  any  certainty ;  but  it  is 
probably  the  same  as  in  simple  jaundice. 

iii.  If  the  jaundice  be  accompanied  or  preceded  by 
attacks  of  severe  shooting  pains  in  the  right  hypochon- 
drium  ;  or  if  the  jaundice  be  intermittent,  one  attack 
quickly  succeeding  the  other,  the  cause  is  probably 
gall-stones. 

iv.  An  intense  persistent  jaundice,  if  approaching 
twelve  months  in  duration,  is  due,  probably  not  to 
cancer,  but  to  gall-stones,  hydatids,  or  stricture  of 
the  duct. 

V.  A  slight  persistent  jaundice  is  probably  due  to 
changes  in  the  texture  of  the  liver,  as  cirrhosis,  nut- 
meg liver,  &c. 

vi.  Jaundice  with  great  enlargement  of  the  liver  is 
probably  due  to  cancer. 

vii.  Jaundice  complicated  with  ascites  is  probably 
due  to  cirrhosis. 

viii.  Delirium  setting  in  during  an  acute  jaundice 
suggests  icterus  gravis. 

Prognosis.  The  length  of  time  which  a  jaundice  may 
last  varies  with  the  cause  of  the  jaundice.  In  one  case, 
the  yellowness  may  be  a  mere  transitory  symptom,  last- 


Prognosis  of  Jaundice.  3  77 

ing  but  a  few  days,  the  conjunctiva  only  being  coloured, 
and  the  urine  just  showing  a  faint  reaction  of  bile  pig- 
ment. In  another,  the  jaundice  may  be  intense  and 
last  three  or  four  years.  Or  the  patient  may  recover 
from  one  attack,  only  on  recovery  to  fall  into  another 
access  of  the  same  disease,  and  this  alternation  of  health 
and  disease  may  last  many  months,  or  even  years.  Such 
a  case  is  reported  by  Van  Swieten,  in  which  a  woman 
had  jaundice  off  and  on  for  12  years.*  Heberden  says 
he  has  known  the  jaundice  return  frequently  for  more 
than  20  years  in  some  persons,  who  have  had  good 
health  in  the  intervals  of  the  fits..  He  also  speaks  of 
a  woman  who  for  five  years  laboured  under  all  the  usual 
symptoms  of  the  jaundice  in  the  highest  degree. f  Dr. 
Joseph  Ayre  speaks  of  a  gentleman  who  had  been  jaun- 
diced for  eight  years  from  a  permanent  obstruction  of 
the  biliary  duct,  J  and  Devay  of  a  woman  who  stated 
that  she  had  been  jaundiced  for  7  years. §  She  was 
only  under  observation  a  few  days  before  death  ;  a 
peasant,  and  of  ^^intelligence  faible  et grossiere,^^  so  that 
but  little  trust  can  be  placed  in  her  statements.  I  have 
myself  seen  a  patient  jaundiced  continuously  for  six 
years  and  a  half,  and  yet  able  to  do  light  work,  such 
as  book-keeping  or  account  keeping. 

How  long  may  a  patient  live  with  the  gall  ducts  com- 
pletely obstructed  ?  Graves  and  Stokes  have  recorded 
a  case  of  jaundice  in  which  the  stools  were  colourless 
for  two  years,  yet  the  appetite  returned,  the  bowels 
became  regular,  and  all  bad  symptoms  disappeared.  |( 
Dr.  Hilton  Fagge  speaks  of  a  case  lasting  7  years  with 

*  Van  Swieten,  Comment.  §  950,  Lugd.  Batav.  1755,  t.  iii.  p.  130.  This  case  is 
usually  quoted  as  if  the  jaundice  had  persisted  for  12  years  without  internriission. 
It  was  continuous  only  for  the  last  of  the  twelve  years. 

f  Heberden,  Commentaries,  Lend.  1806,  Third  ed.  p.  243. 

X  Joseph  Ayre,  Practical  Observations  on  those  Diseases  of  the  Liver,  etc.  Lend 
1821,  p.  16. 

§  Devay,  Gaz.  med.  de  Paris,  1843,  p.  263. 

II  Graves  and  Stokes,  Dublin  Hospital  Reports,  1830.  Vol.  v.  p.  log. 


378  Prognosis  of  Jaundice. 

persistent  jaundice,*  But  there  is  every  reason  to 
think  that  a  case  of  complete  obstruction  to  the  gall 
ducts  rarely  lasts  for  more  than  a  twelve-month.  Very 
few  of  my  own  cases  have  lasted  so  long.  The  matter 
is  of  course  different  when  the  obstruction  is  in- 
complete, or  the  jaundice  intermitting.t  Much  also, 
in  the  length  of  time  which  jaundice  will  last,  depends 
upon  the  nature  of  the  obstruction.  Jaundice  caused 
by  cancer  will,  in  the  usual  course  of  events,  end  more 
quickly  than  that  caused  by  hydatids,  gall  stones,  or 
other  permanent  constriction  of  the  duct. 

The  prognosis  of  jaundice  depends  solely  on  the 
cause.  If  due  to  organic  disease  of  the  liver,  the 
prognosis  becomes  involved  in  the  liver  disease.  If, 
as  in  so  many  cases  of  simple  jaundice,  there  be  no 
apparent  disease  of  the  liver,  the  prognosis  becomes 
exceedingly  favourable  ;  the  immense  majority  of  cases 
of  simple  jaundice  end  in  six  weeks  in  the  complete 
recovery  of  health.  Still,  the  practitioner  can  never 
feel  quite  happy  even  when  attending  the  simplest  case 
of  jaundice,  as  the  beginnings  of  acute  yellow  atrophy 
cannot  in  the  present  state  of  knowledge  be  distin- 
guished from  simple  jaundice.  The  physician  should 
thus  be  on  his  guard  not  to  give  too  confident  a  prog- 
nosis, lest  in  a  few  days  delirium  or  coma  come  on,  and 
his  forecast  falsified. 

The  appearance  of  nervous  symptoms  or  of  hsemor- 
rhages,  whether  in  acute  or  chronic  jaundice,  is  cer- 
tainly of  very  evil  augury,  and  is  most  commonly  the 
forerunner  of  death.  The  same  may  be  said  of  a  rise 
of  temperature.  The  slow  pulse  is  usually  without  in- 
fluence   on   the    prognosis ;    Karl  Ketli  has,   however, 

*  Hilton  Fagge,  Guy's  Hospital  Reports,  1875.  Vol.  xx.  Third  series,  p.  164. 

f  Hertz  has  published  {Berlin,  klin.  Wocliensclirift,  1877,  p.  76)  a  case  with 
details  rather  obscurely  related  in  which  the  same  intermitting  jaundice  was 
noticed  from  Christmas,  1871  to  death  in  April,  1874.  It  would  seem,  but  this  is 
not  at  all  clear,  that  the  jaundice  was  persistent  the  last  two  years  before  death. 


Prognosis  of  Jaundice.  379 

published  a  case  of  jaundice  in  which  death  seemed  to 
take  place  from  the  heart ;  the  pulse  became  slower 
and  slower,  until  the  patient  died.*  Itching  and  xanthe- 
lasma have  no  influence  on  the  prognosis.  Xanthopsy 
and  nyctalopia  are  thought  by  some  to  be  very  bad 
signs. 

The  best  symptom  that  can  be  seen  in  jaundice  is  a 
return  of  colour  in  the  stools.  This  symptom  appears 
first  of  all,  long  before  the  yellow  colour  has  begun  to 
disappear  from  the  conjunctiva,  or  the  urine  to  lose  its 
pigment :  indeed  the  urine,  as  it  is  the  first  to  show  the 
pigment,  so  it  is  often  the  last  to  lose  it.  Care  must  be 
taken  in  judging  of  the  stools  to  be  sure  that  the  colour 
is  due  to  bile,  and  not  to  a  foreign  admixture. 

*  Karl  Ketli,  Wien.  nied.  Wochenschrift,  1878.  p.  135. 


CHAPTER   XVI. 

The  Treatment  of  Jaundice. 

Jaundice  is  but  a  symptom  ;  and  in  its  treatment,  atten- 
tion must  be  first  of  all  paid  to  the  causes  which  bring 
about  the  jaundice.  If  the  jaundice  be  associated  with 
a  gastro-duodenal  catarrh,  this  state  of  the  mucous 
membrane  must  first  be  remedied.  If  the  jaundice  be 
due  to  the  pressure  upon  the  gall  duct  of  hardened 
faeces  in  the  large  intestine,  these  should  be  removed. 
Or  if  due  to  the  passage  of  gall  stones,  the  main  aim  of 
the  physician  will  be  to  render  the  escape  of  the  gall 
stone  from  the  common  duct  more  easy.  If  tumours 
outside  the  liver,  and  these  may  spring  from  any  neigh- 
bouring organ,  press  on  the  gall  ducts,  an  attempt 
should  be  made  to  relieve  the  pressure.  In  jaundice 
from  disease  of  the  liver,  the  disease  of  the  liver  itself 
should  be  treated,  and  the  jaundice  may  almost  be 
neglected.  Thus  the  treatment  of  jaundice  resolves 
itself  into  the  treatment  of  the  disease  causing  the  jaun- 
dice, and  to  this  the  judicious  practitioner  will  com- 
monly restrict  himself. 

But  though  the  treatment  of  jaundice  should  be  left 
to  that  of  the  disease  by  which  it  is  caused,  yet  the  re- 
sults of  the  jaundice,  the  injuries  done  to  the  functions 
of  the  liver,  and  the  consequent  damage  to  the  general 
health,  deserve  some  attention.  The  means  at  our 
disposal  for  the  relief  of  these  states  are  but  feeble,  as 
it  would  be  folly  to  expect  that  the  effect  would  cease 
while  the  cause  is  in  active  operation. 

First,  the  supposed  injury  to  the  digestion  in  the  in- 
testines from  the  lack  of  bile  may  be  considered.  It  is 
doubtful,  however,  if  bile  be  of  any  importance,  save  for 


Rational  Treatment  of  Jaundice.  381 

the  digestion  of  the  fats ;  and  seeing  this,  fat  should  be 
carefully  excluded  from  the  diet  of  the  patient,  if  he  do 
not  instinctively  shun  it.  To  remedy  the  want  of  bile 
in  the  intestine,  it  was  proposed  many  years  ago  by 
Eaglesfield  Smith  to  give  the  bile  of  animals  to 
patients  suffering  from  jaundice,*  and  in  the  present 
day,  ox-bile  is  given,  enclosed  in  capsules,  nicely  regu- 
lated, it  is  said,  to  break  at  the  moment  of  passing  the 
pylorus.  Setting  aside  the  question  whether  they  do 
indeed  melt  at  the  right  moment,  or  whether  they  do 
not  beforehand  discharge  their  contents  in  the  stomach, 
and  thus  upset  the  process  of  gastric  digestion,  experi- 
ence does  not  give  a  very  favourable  account  of  their 
method.  I  have  seen  the  capsules  employed,  and  I  do 
not  think  I  have  noted  any  marked  benefit  follow  their 
use.     Indeed,  it  was  hardly  to  be  looked  for. 

Secondly,  the  damage  done  to  the  liver  itself.  Phy- 
siologists are  not  acquainted  with  any  means  for  artifi- 
cially supplying  glycogen  ;  nor  do  therapeutists  know 
any  remedy  by  which  the  overgrowth  of  connective 
tissue  in  the  liver  may  be  checked.  But  some  attempt 
may  be  made  to  stay  the  wasting  and  aneemia  which 
are  associated  with  the  hindrance  to  the  flow  of  bile 
into  the  duodenum.  Attention  to  the  nutrition  of  the 
patient  formed  a  large  part  of  the  treatment  of  Hippo- 
crates.f  Fatty  foods,  it  has  been  said,  are  improper; 
and  thus  cod-liver  oil  should  be  excluded.  Nitrogenous 
aliments  should  be  chiefly  used  ;  such  as  lean  beef  or 
mutton.  Some  writers  represent  patients  with  jaundice 
as  suffering  from  much  flatulence  ;  and  when  this  is  the 
case,  it  would  certainly  be  proper  to  abstain  from  food 
containing  starch  and  sugar.  If  no  inconvenience  be 
felt  from  wind,  this  kind  of  food  would  be  desirable, 
when  the  direct  supply  of  fat  is  taken  away. 

*  See  above,  p.  135. 

f  Hippocrates,  de  locis  in  homhie,  Cap.  xxviii.  Littre's  ed.  t,  vi.  p.  320. 


382  Rational  Treatment  of  Jaundice, 

The  impoverishment  of  the  blood  should  be  met  by 
giving  some  of  the  neutral  preparations  of  iron,  such  as 
the  reduced  iron ;  or  the  old  steel  wine,  prepared  from 
iron  filings ;  or  Squire's  chloroxyde.  Sometimes  the 
patient  may  with  benefit  be  sent  to  a  chalybeate  spring; 
advice  given  by  Sydenham  two  hundred  years  ago.* 

It  has  been  already  stated  that  the  great  channel  by 
which  the  bile  pigment  and  bile  acids  leave  the  blood  is 
the  urine.  By  the  skin  only  a  very  small  amount  is 
excreted  ;  by  the  other  glands,  nothing.  In  many  cases 
of  jaundice,  the  amount  of  urine  is  much  increased, 
and  it  is  desirable  to  keep  up  an  increased  flow  of 
urine,  a  plain  indication  of  nature,  by  means  of  drugs. f 
The  neutral  salts  of  potash  and  soda,  especially  the 
citrates  and  acetates,  will  be  found  useful,  aided  by 
the  mineral  waters  commonly  used  as  drinks,  such  as 
Seltzer,  or  ApoUinaris.  Frerichs  recommends  lemon 
juice,  one  and  a  half  to  three  ounces  daily,  and  says  it 
has  the  advantage  of  both  aiding  digestion  and  causing 
an  abundant  diuresis.J 

The  activity  of  the  skin  should  be  favoured  by  warm 
clothes  and  warm  rooms,  especially  as  the  temperature 
of  the  body  is  often  low.  Of  the  action  of  Turkish 
baths  in  jaundice  I  have  unfortunately  no  experience. 
They  are  likely  to  further  the  excretion  of  the  colouring 
matters  by  the  skin,  and  at  the  end  of  the  disease  to 
favour  the  disappearance  of  the  yellow  colour.  It  is, 
when  the  obstruction  to  the  ducts  has  been  removed, 
that  the  skin  and  kidneys  may  most  advantageously  be 
stimulated ;  and  at  the  same  time  excretion  of  bile 
may  be  increased  by  doses  of  the  alkaline  benzoates.§ 

»  Sydenham,  Processus.  Integri,  Cap.  xxix.  in  Opera  omnia,  ed.  Greenhill,  p.  583. 

f  Warm  baths  and  diuretics  formed  great  part  of  the  Hippocratic  treatment  of 
jaundice.  (O/.  c/L  pp.  244  and  320.)  Graves  hints  rather  obscurely  at  the  use  of 
diuretics.     {Clinical  Lectures,  Dublin,  1864.  p.  633.) 

X  Frerichs,  Klinik  d.  Leberkrankheitcn,  Braunschweig,  1858.  Bd.  i.  p.  129. 

§  Benzoic  acid  was  recommended    by  C.  Ph.  Falck  of   Marburg   in  cases  of 


Empirical  Treatment  of  Jaundice.  383 

These  salts  are  said  to  rapidly  clear  the  skin  of  colour- 
ing matters. 

Besides  the  rational  treatment  of  jaundice,  there  are 
other,  empirical  methods,  which  have  been  employed 
from  the  earliest  times,  and  of  which  it  is  now  neces- 
sary to  speak.  Amongst  these  stand  purgatives  and 
emetics,  acids  and  alkalies,  and  substances  supposed 
to  have  a  direct  action  on  the  liver,  such  as  the  juice 
of  certain  plants.  Some  of  these  empirical  methods 
of  treatment  are  identical  with  those  which  we  call 
rational. 

i.  Purgatives  have  long  enjoyed  a  great  reputation. 
Calomel  used  formerly  to  be  given  in  all  cases  of  jaun- 
dice, and  physicians  were  not  content  with  giving  it 
merely  as  a  purgative  occasionally,  but  it  was  almost 
a  routine  practice  to  give  mercury  so  as  to  affect  the 
mouth,  and  to  bring  on  salivation.  This  has  doubtless 
caused  it  to  lose  its  reputation,  as  well  as  the  evidence 
lately  offered  that  it  has  no  specific  action  on  the  flow 
of  bile  into  the  intestine.  Podophyllin,  which  is  called 
the  vegetable  mercury,  has,  it  is  said,  a  more  active 
influence  upon  the  secretion  of  bile  ;  but  for  this  very 
reason  it  seems  to  me  undesirable  to  be  used  in  cases 
of  obstruction  to   the  ducts,   or  disease   of  the  liver.* 

Other  purgatives,  besides  mercury  and  podophyllin, 
were  used,  such  as  jalap  and  cream  of  tartar,  sul- 
phate of  magnesia,  aloes,  and  colocynth.  Or  the 
patient  was  sent  to  drink  the  purging  waters  at  Har- 
rowgate,  Cheltenham,  Friedrichshall  or  Piillna.  I 
should,  however,  long  hesitate  before  I  subjected  a 
patient  with  a  chronic  jaundice  to  a  course  of  purgative 

jaundice  and  liver  disease.  {Corr.  Bltt.  d.  Vev.f.  gemcinsch.  Arh.  No.  30.  reported 
in  Canstatt's  Jahrcsbcrichtf.  1S58.  Bd.  v.  p.  126.)  Justi  used  it  with  good  success 
in  the  jaundice  of  children  {ibid.  No.  31.)  but  it  should  be  remembered  that  the 
jaundice  of  children  usually  runs  a  very  favourable  course. 

*  See  the  chapter  on  the  Action  of  Drugs  upon  the  Secretion  of  the  Bile,  pp. 
157,  174  and  178. 


384  Use  of  Emetics  in  Jaundice. 

medicines.  One  purgative  dose  may  be  given  early  in 
the  treatment,  or  perhaps  when  the  bowels  become 
costive  ;  but  a  series  of  purgings  will  lower  the  patient's 
strength,  or  even  do  him  a  serious  damage. 

ii.  Emetics  were  once  greatly  in  vogue  for  the  cure 
of  the  jaundice.*  By  the  act  of  vomiting,  the  liver  and 
gall-bladder  are  pressed  upon  from  three  sides,  and  it 
was  thus  thought  that  the  bile  would  be  forced  out  into 
the  duodenum  through  any  moderate  obstruction.  This 
may  possibly  be  the  case  if  the  obstruction  be  nothing 
but  a  plug  of  mucus ;  for  it  may  be  seen  after  death 
how  slight  a  pressure  on  the  gall  bladder  will  suffice  to 
send  the  bile  into  the  duodenum.  Still,  the  diagnosis 
must  have  attained  a  high  degree  of  certainty  for  such 
violent  remedies  as  emetics  to  be  indicated  ;  for,  if  the 
obstruction  be  a  solid  tumour  pressing  on  the  ducts, 
or  a  cancerous  head  of  the  pancreas,  or  a  large  gall 
stone  firmly  impacted  in  the  ducts,  an  emetic  is  more 
likely  to  cause  a  rupture  of  the  gall  bladder  or  ducts 
than  a  resolution  of  the  obstruction. 

If  the  foregoing  be  a  correct  account  of  the  action  of 
emetics  in  jaundice,  it  is  clear  that  they  are  worse  than 
useless  in  all  cases  of  jaundice  from  disease  of  the  liver 
or  where  the  obstruction  in  the  large  ducts  is  of  a  per- 
manent kind.  The  cases  in  which  emetics  may  be 
most  serviceable  are  those  of  jaundice  caused  by  a  plug 
of  mucus,  or  a  small  easily-moved  gall  stone. 

The  tartar  emetic  has  been  much  lauded.  Frerichs 
says  that  he  found  the  bile  passages  of  dogs  to  whom 
he  had  given  tartar  emetic  empty  and  perfectly  free 
from  bile.f  Still  tartar  emetic  cannot  be  recommended 
in  cases  of  acute  catarrh  of  the  stomach.  It  is  well 
known  that  antimony  and  its  congeners  cause  a  catarrh 

*  Hippocrates  recommends  them.    {Dc  affect,  inter.  Cap.  xxxv.  Littre's  ed.  t.  vii. 
p.  254.) 

f  Frerichs,  op.  cit,  Bd.  i,  p.  131. 


Use  of  A  cids  in  Jaundice.  385 

and  fatty  degeneration  of  the  tubular  glands  of  the 
stomach :  and  it  would  seem  unwise  to  prescribe  a 
drug  which  has  the  power  of  begetting  the  same 
disease  as  that  from  which  the  patient  already  suffers. 
Ipecacuanha  has  also  been  recommended,  and  if  emetics 
be  determined  upon  it  would  seem  preferable  to  anti- 
mony. Sir  Dominic  Corrigan  recommends  it  in  30 
grain  doses  every  other  day.* 

It  would  need  much  stronger  evidence  as  to  the  value 
of  emetics  in  jaundice  than  at  present  exists,  to  persuade 
me  to  recommend  a  course  of  such  treatment  to  a  patient 
suffering  even  from  simple  jaundice. f 

iii.  Acids,  both  mineral  and  vegetable,  have  long  en- 
joyed a  great  reputation  in  the  treatment  of  jaundice  ; 
and  they  may  be  used  without  fear  of  any  of  the  ill 
effects  which  sometimes  accompany  emetics  and  pur- 
gatives. Heberden  says  he  has  known  large  quantities 
of  acid,  such  as  lemon  juice,  gain  the  credit  of  the  cure 
of  jaundice  ;:|:  and  Scott  praises  the  nitro-muriatic  acid 
given  by  the  mouth  or  used  in  the  bath.§  For  this 
latter  purpose  I  can  hardly  recommend  it ;  but  I  think 
I  have  seen  good  follow  doses  of  ten  or  twenty  minims 
of  the  dilute  acid  three  times  a-day.  The  action  of  the 
acid  is  explained  in  different  ways.  Some  think  that 
aqtia  regia  has  a  specific  action  upon  the  liver,  and  ap- 
peal to  Dr.  Rutherford's  observation :  others  think 
that  acids  act  by  irritating  the  duodenal  papilla  as  in 
Claude  Bernard's  well-known  experiment.  || 

iv.  The  alkaline  carbonates  and  soaps  were  formerly 
given,  to  make  amends  for  the  deficiency  of  the  bile,  by 
aiding  the  digestion  and  cleansing  the  bowels.^    At  the 

*  Corrigan,  Dublin  Hosp.  Gaz.  1845,  pp.  69  and  71. 

f  StoU  condemns  the  use  of  emetics  in  jaundice  and  says  he  has  seen  much 
harm  from  them.     {Rat.  Med.  pars  iii.  Viennas,  17S0,  p.  388.) 
X  Heberden,  Commentaries,  London,  1S06,  Third  ed.  p.  259. 
§  H.  Scott,  Med.  Chir.  Trans.  1817,  Vol.  viii.  p.  173. 
II   See  pp.  127  and  173  of  this  work. 
%  Heberden,  loc.  cit. 


386  Use  of  Simples  in  Jaundice. 

present  day  they  are  most  commonly  administered  in 
the  Carlsbad  and  Marienbad  waters.  With  these,  it 
must  be  remembered,  a  large  amount  of  water  is  taken, 
as  well  as  other  salts  besides  carbonates,  but  they 
sometimes  relieve  cases  in  which  other  remedies  had 
been  unsuccessful. 

In  the  early  stages  of  a  jaundice  complicated  with 
gastric  catarrh,  a  mild  alkaline  course  is  often  most 
useful. 

V.  Simples  have  enjoyed  a  great  reputation,  the  foun- 
dation of  which  is  thought  to  have  been  laid  by  Van 
Swieten.  He  treated  a  woman,  60  years  old,  who  had 
been  troubled  with  the  jaundice  for  12  years,  after  the 
following  plan  :  the  juice  of  grass,  milk  whey,  and  the 
like  during  the  spring ;  the  Spa  waters  during  the  sum- 
mer ;  and  Venice  soap  and  honey  during  the  winter. 
For  six  months  she  had  a  cceliac  flux,  and  passed 
abundance  of  small  stones,  with  recovery.*  In  like 
manner  the  juice  of  the  taraxacum  and  of  the  cardnus 
benedictuSj  especially  if  freshly  expressed,  has  been 
much  lauded,  chiefly  by  village  practitioners.!  There 
is,  however,  very  little  evidence  of  the  value  of  these  herbs 
in  the  treatment  of  jaundice. 

Conium,  belladonna,  and  other  anti-spasmodlcs,  were 
much  used  in  the  treatment  of  jaundice  when  it  was 
thought  that  the  symptom  depended  on  spasm  of  the 
gall  ducts  ;  and  with  the  revival  of  a  doctrine  of  icterus 
spasticus  may  come  again  into  fashion. 

*  G.  van  Swieten,  Comment.  §  950.  Lugd.  Eatav.  1755,  t.  iii.  p.  130. 

f  Some  of  the  remedies  for  the  jaundice  used  by  the  public,  and  which  have  in 
a  few  instances  made  their  way  into  pseudo-therapeutic  works,  are  more  interest- 
ing to  the  student  of  folk  lore  than  to  the  physician.  Such  are  the  administration 
of  spiders  and  lice  ;  the  mixing  of  urine  with  honey  and  sugar ;  (Cf.  Pliny,  Nat. 
Hist.  Lib.  XXX.  Cap.  xi.)  making  a  cake  with  the  urine  of  the  patient  and  meal, 
and  giving  it  to  a  dog,  who  must  be  of  the  male  sex ;  or  the  more  loathsome  sug- 
gestion of  dosing  the  patient  with  the  excrements  of  the  goose  ;  a  plan  of  treat- 
ment which  I  believe  the  homceopathists  have  made  their  own,  and  in  the 
possession  of  which  no  one  is  likely  to  disturb  them. 


Treatment  of  the  Complications  of  Jaundice.       387 

With  Bamberger,*  we  may  regret  that  not  a  step 
has  been  made  forward  in  the  treatment  of  jaundice  for 
2000  years,  and  that  the  therapeutics  of  this  age  are,  in 
all  essential  points,  the  same  as  those  of  Hippocrates 
and  the  early  Greeks. 

Treatment  of  the  Complications  of  Jaundice.  The  wast- 
ing has  already  been  spoken  of.  The  patients  are  often 
chilly,  and  complain  of  a  sensation  of  cold :  this  may 
best  be  treated  by  attention  to  the  clothing,  which  should 
be  a  matter  of  care  in  nearly  all  cases  of  jaundice.  The 
high  temperature  which  comes  on  just  before  the  fatal 
ending  of  the  case  should  not,  in  my  opinion,  be  treated. 

The  itching  of  the  skin  is  sometimes  so  severe  that 
narcotics  must  be  given  to  procure  sleep.  I  have  my- 
self seen  the  most  relief  from  mercurial  ointments,  made 
with  calomel  or  white  precipitate.  Sometimes  spirituous 
lotions,  containing  hydrocyanic  acid,  or  carbolic  acid 
and  glycerine,  give  ease.  The  warm  bath  with  friction 
may  also  be  employed. 

The  slow  pulse  and  changes  in  the  senses  do  not 
need  special  treatment. 

The  setting  in  of  hsemorrhages  is  of  bad  omen,  and 
little  can  be  done  by  way  of  treatment. 

Gallic  acid  and  tannic  acid  may  be  used  internally 
and  externally ;  or  large  doses  of  the  tincture  of  iron, 
or  turpentine  may  be  given.  If  the  bleeding  be  from 
the  nose,  and  very  abundant,  it  would  be  right  to  plug 
the  nares. 

Like  the  haemorrhages,  the  appearance  of  nervous 
symptoms  is  a  bad  sign.  I  have  seen  advantage  in 
these  cases  from  active  purging  ;  but  severe  treatment 
such  as  blisters  to  the  head  or  nape  of  the  neck,  leeches, 
hourly  doses  of  calomel,  and  the  like,  cannot  be  recom- 
mended. 

The  xanthelasma  should  remain  untreated. 

*  Bamberger,  KranhhcUcn  dcs  chylopoct.  Systems,  Erlangen,  1864,  p.  484. 

CC  2 


CHAPTER   XVII. 

Icterus  Simplex. 

Synonyms.     Icterus  communis,  benignus,  catarrhalis,  gas- 
troduodenalis,  duodenalis,  spasmodiciis,  spasticus,  vernalis. 

Simple  jaundice  is  a  mild  disorder  which  runs  a  quick 
course  towards  recovery,  and  which  shows  no  signs  of 
any  notable  disease  in  any  organ,  even  in  the  liver  itself. 

This  jaundice  has  been  known  and  described  from 
the  earliest  times,  but  it  cannot  be  said  that  its  nature 
and  cause  are  even  now  beyond  a  doubt. 

It  is  by  far  the  most  common  of  all  the  varieties  of 
jaundice  ;  it  is  probable  that  it  is  oftener  seen  than  all 
the  other  varieties  added  together. 

A  surfeit  of  food,  especially  if  indigestible,  and,  above 
all,  a  fit  of  drunkenness,  are  apt  to  be  followed  by  a 
gastric  catarrh  and  a  jaundice.  In  these  cases  the  aeti- 
ology of  the  jaundice  would  be  said  by  many  to  be  clear. 
In  some  the  vomiting  may  come  on  after  exposure  to 
bad  smells,*  or  other  unwholesome  influences,  as  is 
well  seen  in  cases  of  simple  jaundice,  which,  when  nu- 
merous enough,  are  called  epidemic  jaundice,  but  are 
not  uncommonly  seen  in  single  cases.  Then  there  is  a 
jaundice  which  follows  mental  emotions  of  all  sorts,  the 
old  icterus  ex  inotu  animi.  This  cause  of  jaundice  is 
said  to  be  so  firmly  held  by  the  vulgar  in  Germany  that 
all   cases  are  unhesitatingly  set  down  to  mental  emo- 

*  Powell  {Observations  on  the  Bile  and  its  Diseases,  Lond.  1800.  p.  77)  says  that 
medical  students  are  often  seized  with  the  jaundice  soon  after  they  begin  to  work 
in  the  dissecting  room.  Powell  seems  to  attribute  this  to  the  posture  and  confine- 
ment necessary  for  this  study.  I  have  not  myself  observed  medical  students  to  be 
more  often  jaundiced  than  others  ;  but  if  it  were  a  fact,  I  should  attribute  it  rather 
to  the  bad  sanitary  state,  as  I  have  often  seen  persons  exposed  to  bad  smells  and 
the  like,  jaundiced. 


Ictenis  ex  motu  animi,  389 

tion.*  In  the  older  writers  there  will  be  found  many 
cases  of  jaundice  immediately  following  great  mental 
emotion  ;t  there  are  cases  of  ■  prisoners  becoming 
yellow  at  the  moment  that  sentence  of  death  was 
pronounced  upon  them ;  of  two  young  men  about  to 
fight  a  duel,  when  one  of  them  saw  the  other  become  so 
yellow,  that  being  astonished,  he  ceased  to  fight  ;  of  a 
young  priest,  frightened  by  a  dog,  falling  half  dead,  and 
being  taken  up  yellow  as  saffron :  of  a  young  soldier, 
who,  being  struck  in  a  public  place,  attempted  to  return 
the  blow,  but,  being  hindered  by  the  bystanders,  be- 
came jaundiced  almost  at  that  instant,  and  soon  after 
fell  into  a  fever  and  delirium,  and  died  in  the  midst  of 
convulsions.  J  All  these  cases  seem  to  me  capable  of 
quite  a  different  interpretation  ;  the  pallor  caused  by 
excessive  fear  is  often  yellov/ish  ;  and  may  have  been 
easily  mistaken  by  inexperienced  or  careless  observers 
for  a  true  jaundice. §  In  none  of  the  cases  does  a  care- 
ful examination  seem  to  have  been  made  ;    nothing  is 

*  Frerichs,  Klinik  d.  Lebcrkranklieiten,  Braunschweig,  1858.  Bd.  i.  p.  166  note. 
The  same  notion  prevailed  in  England  ;  as  Shakspere  can  testify ; 

"  Creep  into  the  jaundice 
by  being  peevish." 

Merchant  of  Venice,  I.  i. 

"  What  grief  hath  set  the  jaundice  on  your  cheeks  ? 

Troilus  and  Cressida,  I.  iii. 

f  I  do  not  think  that  Horace  meant  to  speak  of  jaundice  when  he  describes  the 
following  effect  of  jealousy : 

Quum  tu,  Lydia,  Telephi 

Cervicem  roseam,  cerea  Teleph 
Laudas  brachia,  vs  meum 

Fervens  difficili  bile  tumet  jecur. 

{Carm,  Lib.  i.  Od.  xiii.)  The  poets  contain  many  allusions  to  the  liver,  as  it  was 
the  seat  of  the  emotions,  love,  courage,  &c. 

X  Portal,  Observations  sur  la  nature  et  le  traitemcnt  dcs  maladies  dufoie,  Paris, 
1813.  p.  141. 

Villeneuve,  Diet,  dcs  Scicnees  mcd.  Paris,  1818.  t.  xxlii.  p.  419. 

§  The  jaundice  described  by  Sydenham  {Obs.  Med.  iv.  7.  Greenhill's  ed.  p.  202) 
as  seen  in  hypochrondriac  men  and  hysterical  women,  must,  I  venture  to  think,  be 
put  down  to  gall  stones  rather  than  a  nervous  affection.  In  this  opinion  Heberden 
shares:  "No  reasonable  deference  to  this  accurate  observer  can  make  anyone 
much  doubt  of  his  having  been  mistaken."     {Comm.  Lond,  1806.  Third  ed.  p.  240.) 


390  Symptoms  of  Simple  Jaundice, 

said  about  the  conjunctiva  or  the  state  of  the  urine.  It 
is,  however,  otherwise  with  the  cases  in  which  an  inter- 
val, of  days  or  weeks  perhaps,  comes  between  the  emo- 
tion and  the  appearance  of  the  jaundice.  To  these 
credence  may  be  given,  though  whether  the  emotion  be 
a  cause  of  the  jaundice  remains  to  be  discussed.  Some 
of  these  cases  are  quite  classical,  and  are  quoted  every- 
where.* 

Sir  Thomas  Watsonf  and  Dr.  Bence  JonesJ  sup- 
ported the  theory  that  mental  emotion  was  a  cause  of 
jaundice. 

In  certain  cases  no  cause  whatever  can  be  discovered. 
The  season  of  the  year  has  some  influence  ;  simple 
jaundice  is  more  comm_on  in  the  spring  and  fall,  parti- 
cularly the  autumn. 

In  simple  jaundice,  the  first  notice  that  the  patient  is 
ill  is  often  the  sight  of  his  own  face  in  the  glass,  or  the 
being  told  by  others  of  his  yellow  colour.  This  may 
happen  on  rising  in  the  morning,  and  the  patient  then 
finds  that  he  has  lost  appetite  and  feels  sick ;  or  he 
may  even  vomit.  In  a  certain  number  of  cases,  the 
gastric  symptoms  come  on  later,  even  three  or  four 
days  after  the  jaundice.  In  other  cases,  the  greater 
number,  perhaps,  the  gastric  symptoms  appear  before 
the  jaundice,  a  day,  a  week,  or  even  longer. 

When  the  gastric  symptoms  are  not  marked,  there 
are  sometimes  signs  of  an  intestinal  catarrh,  diarrhoea, 
or  tape  worm,  and  the  like. 

*  Dr.  Wilks  has  recorded  a  case  of  jaundice  which  he  appears  to  think  due  to 
emotion,  the  patient  having  been  much  frightened  five  days  before  the  jaundice 
came  on.  There  were,  however,  at  the  same  time,  headache,  nausea,  and  slight 
diarrhoea.  {By'it.  Med.  yournal,  1870.  Vol.  ii.  p.  4.)  In  the  same  volume  (p.  547) 
Mr.  Churton  has  published  a  case  in  which  "  acute  hepatic  pain  "  and  mental  disturb- 
ance came  together.  The  jaundice  was  treated  with  bromide  of  potassium,  and 
recovery  seems  to  be  attributed  to  the  use  of  this  remedy.  Dr.  A.  W.  Foot  {Dub- 
lin yournal  of  Med.  Science,  1874.  Vol.  Ivii.  p.  217)  and  Ferber  {Arch.  d.  Hcilkunde, 
1868.  p.  558)  have  also  published  cases  which  they  set  down  to  emotional  causes. 

f  Sir  Thomas  Watson,  Lectures  on  the  Principles  and  Practice  of  Physic,  Lonil. 
1857.  4th  cd.  vol.  ii.  p.  609. 

\  Bcncc  Jones,  S.  George's  Hosp.  Reports,  1S66.  vol.  i.  p.  193. 


Symptoms  of  Simple  Jaundice.  391 

Frerichs  found  that  out  of  41  cases  of  simple  jaundice 
symptoms  of  a  gastro-intestinal  catarrh  were  present  as 
prodroma  in  34.*  In  my  own  cases,  the  proportion  is 
nothing  so  great ;  but  my  figures,  I  must  own,  prove 
little  or  nothing.  They  were  taken  from  out-patients  ; 
and  many  of  the  cases  I  saw  only  twice  or  three  times, 
so  that  I  was  unable  to  verify  my  diagnosis  by  seeing 
the  recovery  of  the  patient. 

It  must  be  owned  that  in  certain  cases,  no  other 
symptom  save  that  of  jaundice  can  be  found  out.  The 
patient  says  that  he  is  in  good  health,  saving  only  his 
yellow  appearance,  and  applies  for  medical  help  purely 
on  account  of  his  yellow  colour. 

With  the  gastric  symptoms  there  commonly  set  in, 
especially  with  women,  giddiness,  headache,  and  a 
sense  of  weakness  or  feebleness,  which  may  be  so 
great  that  a  febrile  disorder  may  be  thought  of, 
typhoid  or  the  like.  There  is  not  unfrequently  a 
slight  rise  in  the  temperature,  which  rarely  passes 
above  100°.  The  tongue  is  usually  coated  with  a 
white  fur ;  there  may  be  diarrhoea  or  constipation, 
and  the  faeces  are  colourless.  The  pulse  usually  pre- 
serves its  natural  number  of  beats.  In  women  it  may 
even  be  a  little  quicker  ;  in  some  cases  it  becomes 
slow,  as  60  or  65  ;  and  in  rare  cases  it  may  sink  lower, 
even  to  40.     Itching  is  often  seen  ;  xanthopsy  rarely. 

On  physical  examination,  the  liver  will  as  a  rule  be 
found  slightly  enlarged,  and  the  right  hypochondriac 
and  epigastric  regions  somewhat  tender  to  pressure. 
Gerhardt  has  pointed  out  the  importance  of  being 
able  to  feel  or  percuss  the  enlarged  gall  bladder,t 
this,  however,  is  not  always  possible  ;  as  the  shape  and 
position  of  the  reservoir  are  not  constant.     When  made 

*  Frerichs,  Klinik  d.  Lchcrkranhhcitcn,  Braunschweig,  1861.  Bd.  ii.  p.  418. 
f  Gerhardt,  Ucbcr  Icterus  gastro-duodcnalis,  in  Volkmann's  Saininlung  klinis- 
cher  Vortrdgc,  Leipzig,  1870-75,  p.  107. 


392       Simple  Jaundice  due  to  obstruction  of  the  Ducts. 

out,  it  is  an  important  sign  of  obstruction  to  the  common 
duct. 

Bamberger  states  that  pulmonary  catarrh  is  very 
often  an  accompaniment  of  this  simple  jaundice.* 

A  simple  jaundice  always  ends  in  recovery,  and  the 
first  sign  of  convalescence  is  said  to  be  a  return  of  the 
appetite.  Bamberger  notes  during  convalescence  a 
fames  canina  like  that  seen  after  typhoid. 

The  disease  may  last  as  short  a  time  as  a  week  or  ten 
days ;  or  be  prolonged  to  three  and  even  four  months. 
After  two  months,  great  suspicion  m.ust  rest  on  the 
diagnosis.  The  average  appears  to  be  three  to  four 
weeks. 

As  the  disease  never  ends  in  death,  but  always  in 
recovery,  there  are  no  opportunities  for  examining  the 
cause  of  the  jaundice  by  the  help  of  anatomy,  unless 
the  life  of  the  patient  be  ended  by  accident  or  some 
other  disease  ;  in  this  last  case  the  observation  will  not 
be  quite  free  from  suspicion.  The  cause  of  the  jaun- 
dice therefore  remains  unknown,  and  it  is  only  by  a 
comparison  with  like  diseases  and  states,  that  any  light 
can  be  thrown  on  the  matter. 

One  point  only  is  tolerably  certain ;  that  the  bile 
does  not  find  its  way  into  the  duodenum,  as  shown  by 
the  colourless  state  of  the  stools ;  and  in  those  cases 
in  which  the  gall  bladder  is  found  distended,  it  may  be 
asserted  that  the  hindrance  is  in  the  common  duct. 
All  beyond  this  is  little  better  than  conjecture. 

The  conjecture  which  found  greatest  favour  during 
the  last  century  as  an  explanation  of  simple  jaundice, 
was  the  view  that  there  was  a  spasmodic  contraction  of 
the  bile  ducts.  This  contraction  became  so  great  that 
it  was  impossible  for  the  bile  to  pass  down  the  ducts, 
no    cavity   being    left,    but    merely  a    solid   ligament. 

•  Bamberger,  Krankhcilcn  dcs  chylopoclischcn  Systems,  in  Virchow's  Handb.  d. 
spec.  Path.  u.  Titer.  Erlangen,  1864.  2tc  Aufl.  p.  566. 


Icterus  spasticHS.  393 

After  death,  the  spasm  relaxed,  and  no  traces  of  its 
existence  could  be  found  in  the  body.  This  idea  of  an 
icterus  spasmodiciis  or  spasticus  would  explain  all  those 
cases  in  which  no  palpable  obstruction  to  the  ducts 
was  discovered,  and  could  therefore  be  applied  to  those 
for  which  now-a-days  the  theory  of  a  haematogen- 
ous  jaundice,  or  the  like,  is  brought  in.  The  exis- 
tence of  a  spasmodic  jaundice  was  accepted  by  Peter 
Frank,*  and  many  others  ;  Cullen  says  :  "  such  spasm 
may  happen  either  in  the  duct  itself,  which  we  suppose 
to  be  contractile,  or  in  the  duodenum  pressing  the  sides 
of  the  duct  close  together. f"  The  theory  was  used  by 
Briining  to  explain  the  appearance  of  icterus  epidemius, 
and  has  continued  down  into  our  own  time  in  vogue  as 
a  possible  explanation  of  some  kinds  of  jaundice. J  It 
may  be  found  even  now  spoken  of  here  and  there  by 
certain  French  authors. §  Sir  Thomas  Watson  says  we 
can  neither  prove  nor  disprove  it.|| 

*  Peter  Frank,  de  cur.  hoiii.  morb.  epitome,  Viennse,  1821,  Lib.  vi.  Pars  iii.  p. 
320. 

f  CxiWen,  First  Lines  of  the  Practice  of  Physic,  §  mdcccxviii,  Thomson's  edi- 
tion, Vol.  ii.  p.  656. 

\  Briining,  de  ictero  spasmodico  cpidemico  infantum  EssendicE,  Vasal,  et  Lips. 
1773,  quoted  by  Joseph  Frank,  Prax,  ined.  univ.  prcuc.  Lips.  1843,  Pars  iii. 
Vol.  ii.  Sect.  ii.  t.  i.  p.  311. 

§  Gubler,  Gaz.  mcd.  de  Paris,  1854,  p.  218. 

II  Watson,  Lectures  on  the  Principles  and  Practice  of  Physic,  Lond.  1857,4th  ed. 
Vol.  ii.  p.  609. 

Howship  has  recorded  a  case  in  which  he  thinks  he  detected  constriction  of  the 
ducts  after  death.  A  young  man,  aged  18,  died  after  48  hours  of  excruciating 
pain  in  the  seat  of  the  gall-bladder.  After  death  the  liver  was  found  quite  natural, 
the  gall-bladder  large,  tense,  and  full.  The  large  and  small  intestines  contained 
a  white  mucous  matter,  but  no  trace  of  bile.  The  ductus  communis  being  punctured 
with  a  lancet  about  its  middle,  a  very  small  probe,  with  some  difficulty,  passed 
through  it  into  the  bowels.  In  the  opposite  direction  it  passed  with  tolerable  ease 
by  the  hepatic  duct  into  the  liver.  Howship  found,  dissecting  still  further,  the 
impervious  duct  solid,  contracted,  tough,  and  opaque,  like  a  soft  ligamentous  struc- 
ture. After  six  hours  and  later  the  ducts  had  become  perfectly  relaxed.  (Practical 
Remarks  on  the  Discrimination  and  Appearances  of  Surgical  Disease,  London,  1840. 
p.  194.; 

There  is  no  mention  of  delirium  ;  the  skin  was  mottled  as  in  scarlatina  with  an 
appearance  of  petechiae ;  spots  of  blood  in  the  stomach  under  the  villous  lining. 
It  was  not  apparently  a  case  of  icterus  gravis. 


394  Contractile  Fibres  in  the  Gall  Ducts. 

The  hypothesis  of  icterus  spasmodicus  depends  on  the 
possible  irritabiHty  of  the  bile  ducts,  and  the  hypothesis 
has  therefore  risen  or  fallen  in  favour  according  to  the 
views  taken  of  the  presence  of  muscular  fibres  in  the 
ducts  leading  from  the  liver. 

It  still  seems  to  be  an  open  question  whether  the 
ducts  can  be  excited  to  contraction  and  whether  they 
contain  involuntary  muscular  fibres. 

Magendie  gave  a  great  blow  to  the  theory  when  he 
stated  that  he  had  never  been  able  to  see  a  trace  of 
contraction  in  the  gall  ducts  of  mammals  after  any 
excitant.*  It  is  denied  by  manyf  that  the  ducts  con- 
tain any  contractile  elements  ;  and  those  who  do  admit 
that  muscular  fibres  are  present,  state  that  the  develope- 
ment  is  very  small  and  that  it  is  not  likely  that  they 
would  be  able  to  affect  the  bore  of  the  duct. J  Others 
maintain  that  the  ducts  are  irritable,  and  contract  on 
the  application  of  various  stimuli. § 

Heidenhain  was  induced,  from  the  irregularity  with 
which  the  bile  made  its  appearance  in  some  of  his 
biliary  fistulas,  to  enquire  if  the  ducts  really  possessed 
contractile  fibres.  He  thinks  he  has  proved  their  exis- 
tence. He  placed  the  ducts,  fresh  from  the  animals,  in 
a  large  volume  of  absolute  alcohol  for  24  hours ;  sections 
were  laid  for  a  few  hours  in  chloride  of  palladium.  (i:goo) 
In  a  few  hours,  the  sections  were  mounted  in  water 
or  glycerine.  The  cylindrical  epithelium  could  be  seen 
well  preserved.     Under  it  was  a  well-marked  layer  of 

*  Magendie,  Precis  elcmentaire  de  Physiologic,  Paris,  1836,  46  ed.  t.  ii.  p.  475. 

f  Henle,  Handb.  d.  system.  Anat.  dcs  Menschcii,  Braunschweig,  1866,  Bd.  ii. 
p.  217.  Frey,  Handb.  d.  Histologic  u.  Histochemic,  Leipzig,  1867,  p.  553. 
Cruveilhier,  Traite  d'anatomie  descriptive,  Paris,  1865-68,  t.  ii.  p.  201. 

X  Kolliker,  Handb.  d.  Gewebclchre  dcs  Menschen,  Leipzig,  1867,  5te  Auflage, 
p.  440.     Leydig,  Lchrb.  d.  Histologic,  Frankfurt  a.  M.  1857.  p.  356. 

§  Longet,  Traite  de  Physiologic,  Paris,  i86g,  30  ed.  t.  ii.  p.  308.  Colin,  Traite 
de  Physiologic  conip.  Paris,  1871,  2e  ed.  t.  i.  p.  785.  Colin  admits  that  the  con- 
traction is  so  feeble  that  no  change  in  the  diameter  of  the  tube  would  be  brought 
about.  Henle  {loc.  cit.)  was  unsuccessful  in  his  attempt  to  cause  contraction  of 
the  ducts  in  a  man  recently  beheaded. 


Contractile  Fibres  in  the  Gall  Ducts.  395 

a  yellow  colour,  the  elements  of  which  ran,  for  the  most 
part,  in  a  circular  direction,  and  in  which  numerous 
long  nuclei  were  visible.  Abundance  also  of  longitu- 
dinal elements  could  be  seen,  not,  however,  clearly 
separated  from  the  circular.  The  elements  in  the 
bundles  of  these  circular  fibres,  might  readily  be  taken 
for  lymphoid  cells,  as  there  was  often  seen  plainly  a 
dark  nucleus  surrounded  by  brighter  cell  substance. 
With  this  marked  layer  was  also  a  certain  amount  of 
connective  tissue. 

If  it  be  true,  as  F.  E.  Schulze  teaches,  that  only  the 
contractile  fibres  are  coloured  yellow  by  palladium, 
then  it  follows  that  the  thick  well-marked  layer,  de- 
scribed by  Heidenhain,  is  made  up  of  these  fibres. 

Heidenhain  also  noted,  in  an  experiment  on  a  rabbit, 
that  the  flow  of  bile  was  much  increased  when  the 
aorta  was  compressed.  Now  this  may  mean  that  the 
ducts  of  the  liver  contracted,  as  contractions  of  the 
bowels  and  uterus  are  also  noted  whenever  the  aorta  is 
compressed.* 

Audige  has  reviewed  the  evidence  of  the  contrac- 
tility of  the  ducts,  and  like  Heidenhain,  has  come 
to  the  conclusion  :  i.  that  there  are  muscular  fibres  in 
the  bile  ducts  both  of  men  and  dogs  ;  and  ii.  that  the 
ducts  of  dogs  show  a  notable  contraction  under  the 
stimulus  of  electricity,  or  mechanical  means.  Audige, 
nevertheless,  will  not  admit  of  a  spasmodic  jaundice  ; 
but  applies  his  view  of  spasm  of  the  ducts  to  the  cases 
in  which  a  gall  stone  is  coming  down  from  the  bladder. f 
Dujardin-Beaumetz  has  indorsed  Audige's  observa- 
tions.J 

It  will  be  seen,  therefore,  that  even  those  who  assert 
the  existence  of  muscular  fibres  in  the  ducts,  and  their 

*  Heidenhain,  Studicn  des  phys.  Inst,  zu  Breslau,  Leipzig,  i86S.  Heft  iv. 
pp.  242-246. 

f  Audige,  Rcchcrchcs  expcrimentales  stir  le  spasme  des  voles  biliarcs,  Paris,  1874. 
X  Dujardin-Beaumetz,  Bulletin  de  Therapeutique,  1873.  t.  Ixxxv.  p.  385. 


39^  Paralytic  Jaundice. 

contractile  power,  do  not  allow  of  the  theory  ol  icterus 
spasmodicns.  Still,  nervous  influences  upon  the  liver 
must  not  be  lost  sight  of,  so  long  as  injury  to  the 
fourth  ventricle  of  the  brain,  or  to  the  sympathetic 
in  the  neck  may  work  such  results.  It  is  true  that 
it  is  the  only  instance  known  ;  but  the  influence  of  the 
nervous  system  upon  the  functions  of  the  liver  would 
probably  form  a  rich  field  of  research  for  the  physiolo- 
gist.* Vulpian  believes  that  jaundice  from  emotion 
may  be  caused  by  a  catarrh  of  the  ducts,  by  an  abun- 
dant polycholia,  or  by  an  inversion  of  the  movement  of 
the  bile  generated  in  the  liver  cells.  He  thinks  it  likely 
that  the  jaundice  is  catarrhal  in  the  greater  number. f 

By  the  side  of  the  spasmodic  jaundice  may  be  con- 
sidered the  paralytic  jaundice,  which  was  once  thought 
to  be  due  to  a  stagnation  of  the  bile  in  the  ducts,  brought 
about  by  the  gall  ducts  and  gall  bladder  not  having  con- 
tracted to  expel  their  contents. J  This  theory  of  jaun- 
dice was  used  by  Th.  von  Dusch  as  an  explanation  of 
acute  yellow  atrophy,  the  cells  of  the  liver  being  dis- 
solved in  the  accumulated  bile.§  Both  these  theories 
are  now  discredited. 

Another  explanation  of  the  cause  of  simple  jaundice, 
held  in  much  favour  at  the  present  day,  is  that  it  is  due 
to  an  extension  of  the  catarrh  of  the  duodenum  and 
stomach  to  the  common  duct.  The  presence  of  symp- 
toms of  gastric  disturbance  undoubtedly  lends  much 
colour  to  this  theory ;  and  in  my  opinion  it  is  in  no  way 
discredited  by  the  criticisms  of  See,  which  are  to  the 


*  Heidenhain  (or  his  pupils,  Arch.  f.  Anat.  nnd  Phys.  i86o.  p.  667)  is  inclined 
to  admit  of  an  icterus  spasticus,  chiefly  because  the  pressure  under  which  the  bile 
passes  down  the  ducts  is  so  small,  and  thus  even  a  slight  constriction  would  be 
enough  to  cause  jaundice. 

f  Vulpian,  Cours  stir  la  Bile,  1874.  Paris,  recueilli  par  Paulicr,  p.  139. 

J  Erasmus  Darwin,  Zoonomia,  Vol.  ii.  §  xxx.  Lond.  iSoi.  Third  ed.  p.  3. 

§  Th.  V.  Dusch,  UntcrsuchiDigcn  u.  Expcriiiicnte  als  Bcilrag  zur  Pathogciics  dcs 
Icterus,  Leipzig,  1854.  p.  37. 


Catarrhal  Jaundice.  397 

effect  that  the  stomach  symptoms  are  not  always  those 
of  gastric  catarrh.*  This  is  quite  true  ;  and  there  are 
some  cases  of  simple  jaundice  in  which  there  are  no 
gastric  symptoms  whatever. 

It  is  commonly  said  by  the  Germans  that  Stokes 
of  Dublin  was  the  first  to  teach  the  theory  of  icterus 
catarrhalis ;  but  it  certainly  seems  that  van  Swieten  had 
some  notion  of  the  doctrine.  He  attributes  the  jaun- 
dice of  the  new-born  to  the  thick  meconium  adhering 
to  the  walls  of  the  duodenum  ;  and  says  that  even  in 
grown-up  people  a  mucous  secretion  remaining  in  the 
upper  part  of  the  intestine  has  been  the  cause  of  jaun- 
dice ;  and  he  gives  the  old  quotation  from  Hippocrates 
to  show  that  jaundice  arising  from  phlegm  is  little 
dangerous  and  easily  cured. f 

It  is  sometimes  said  that  Dr.  John  Hunter  (not  to  be 
confounded  with  the  great  John  Hunter,  the  Surgeon,) 
spoke  of  jaundice  from  catarrh  or  mucus  in  the  ducts. 
He  is  speaking  of  the  cause  of  the  jaundice  in  remittent 
fever  and  says  :  "In  the  body  of  a  person  who  died  of 
pulmonary  consumption,  I  had  lately  occasion  to  ob- 
serve some  things  not  altogether  foreign  to  the  present 
subject.  A  few  days  before  death,  to  the  common 
symptoms  of  the  disease,  was  superadded  a  jaundice. 
The  lungs  were  found  diseased  in  the  usual  manner ; 
there  were  adhesions  to  the  pleura,  tubercles,  indura- 
tions, and  suppurations  in  their  substance.  In  the 
abdomen  there  were  marks  of  superficial  inflammation 
all  over  the  liver,  and  the  lower  surface  of  it  was  united 
to  the  stomach  by  adhesions.  The  gall-bladder  was 
full,  but  no  bile  could  be  squeezed  out  of  it.  On  laying 
the  ductus  communis  open  from  the  duodenum,  it  was 
found  filled  with  bile  of  a  brown  colour,  and  of  a  thick 

*  See,  Gaz.  d.  Hop.  1872.  p.  201. 

f  G.  van  Swieten,  Comment.  §  950.  Lugd.  Bat.   1755.  t.  iiJ.  p.  12S.     "  Imo  et  in 
adultis  pituitosa  colluvies  in  primis  viis  hjerens,  icteri  causa  fuit," 


398  Icterus  gastro-duodenalis. 

and  ropy  consistence,  as  were  also  the  ductus  hepatici. 
Part  of  the  ductus  cysticus  was  laid  open,  and  the  gall- 
bladder was  pressed  with  considerable  force,  but  still  no 
bile  flowed.  Through  a  blow-pipe  introduced  into  the 
duct,  the  air  at  last  with  some  difficulty  was  forced  into 
the  gall-bladder,  after  which  by  pressing  again,  a 
coagulum  of  bile  was  squeezed  out,  and  what  followed 
was  ropy  and  black,  like  melasses.  On  laying  the  duct 
open  all  the  way  to  the  bladder,  there  appeared  no  other 
obstruction  to  the  bile  than  the  coagulum,  which,  as 
well  as  the  thick  and  ropy  state  of  that  secretion,  ap- 
pear rather  to  have  been  the  effects  of  stagnation  than 
a  cause  of  obstruction  in  the  first  instance.  Did  the 
inflammation  in  the  neighbourhood  of  the  ducts,  and 
perhaps  extending  to  them,  excite  such  contractions  in 
them  as  obstructed  the  bile,  in  the  same  way  that  a 
suppression  of  urine,  is  sometimes  a  consequence  of  in- 
flammation, in  the  urinary  passages  ?"* 

Portal  also  says  that  a  swelling  of  the  duodenal 
glands  from  inflammation  or  any  other  cause,  may 
bring  about  a  jaundice  by  hindering  the  flow  of  bile 
into  the  duodenum. f 

When  Broussais  taught  that  all  diseases  were  more 
or  less  due  to  gastritis  or  duodenitis,  it  was  necessary 
that  diseases  of  the  liver  and  ducts  should  follow  the 
rest.  Andral  is  one  of  the  writers  who  have  carried 
out  this  view.  Several  times,  he  says,  he  has  found  in 
the  bodies  of  jaundiced  persons  no  other  change  than  a 
violent  inflammation  of  the  duodenum,  which  appeared 
to  have  extended  to  the  bile  ducts.:}: 

It  was  maintained  by  Stokes  in  his  Lectures  on 
Medicine,  that  the  most  important  and  most  frequent 

*  John  Hunter,  M.D.  Ohscrvalions  on  the  Diseases  of  the  Army  in  jfaniaiea,  Lon- 
don, 1796,  See  Ed.  p.  158. 

f  Portal,  Observations  sur  la  nature  ct  Ic  iraitentent  des  maladies  dii  fvie,  Pan's, 
1813,  p.  154. 

+  Andral,  Cliniqne  vied.  Paris,  1S39,  46  ed.  t.  ii.  p.  290. 


Icterus  gastro-ditodenalis.  399 

cause  of  jaundice  was  disease  of  the  mucous  surface  of 
the  stomach  and  duodenum.  It  is  not,  however,  due  to 
any  mechanical  hindrance  to  the  flow  of  bile,  but  to  a 
"sympathetic  irritation"  of  the  liver,  secondary  to  the 
gastritis.  The  biliary  secretion  is  arrested.  Stokes' 
theory  is  thus  nothing  more  than  the  theory  of  jaundice 
by  suppression,  but  the  suppression  is  due  to  "sympa- 
thetic irritation"  of  the  liver  from  the  stomach.*  Budd, 
on  the  other  hand,  really  noticed  a  catarrhal  plugging 
of  the  ducts:  "It  happens,  however,  not  very  unfre- 
quently,  that,  on  squeezing  the  hepatic  ducts,  a  viscid 
whitish  fluid  oozes  out,  which,  on  examina.tion  through 
the  microscope,  is  seen  to  be  chiefly  made  up  of  the  pris- 
matic epithelial  cells  of  the  gall  ducts. "+  Further: 
"many  of  the  cases  of  simple  jaundice  coming  on  in 
healthy  persons  are  probably  cases  of  this  kind."  But 
later  on  he  says:  "In  a  large  proportion,  perhaps  in 
the  greater  number  of  cases,  jaundice  results  primarily 
and  solely,  from  the  secretion  of  bile  being  suppressed 
or  deficient."^  This  explanation  of  simple  jaundice 
as  a  jaundice  by  suppression  was  in  great  vogue 
twenty  years  ago,  and  even  now  traces  of  the  doctrine 
may  be  met  with,  rather,  however,  in  speech  than  in 
print. 

But  the  writer  who  has  done  the  most  to  advance 
catarrh  of  the  bile  ducts  as  a  cause  of  simple  jaundice 
to  the  favour  in  which  it  is  now  held  by  so  many,  is 
Virchow.  This  is  another  instance  of  a  man,  later  on 
in  life,  destroying  the  work  of  his  earlier  days ;  for  if 
the  theory  of  haematogenous  jaundice  were  received  by 
any  one,  it  was  owing  to  the  support  which  Virchow  gave 
to  it  thirty  years   ago,  on  his  entrance  into  life.§     But 


*  Stokes,  Lond.  Med.  and  Surg,  jfounial,  1834.  vol,  v.  p.  198. 

f  Budd,  0)1  Diseases  of  the  Liver,  London,  1845.     First  edition,  p.  150. 

X  Budd,  op.  cit.  p.  383. 

§  Virchow,  Gcsamin.  Abhandl.  Hamm,  1862,  2te  Aufl.  p.  849. 


400  Vieivs  of  Virchow  and  Glax. 

in  1865,  Virchow  declared  himself  in  favour  of  the 
doctrine  that  jaundice  arises  always  from  the  absorption 
of  bile  secreted  beforehand,  and  showed  from  his  ex- 
perience that  in  many  cases,  unsuspected  before,  a 
catarrh  of  the  ducts,  or  at  least  some  obstruction  to 
them,  might  be  seen  after  death,  if  it  were  only  care- 
fully looked  for.*  This  was  at  once  taken  up  and 
applied  afresh  to  the  explanation  of  simple  jaundice, 
and  it  certainly  seems  to  me  the  best  of  all  the  theories 
which  have  yet  been  proposed.  That  a  catarrh  is  a 
common  cause  of  jaundice  cannot  I  think  be  disputed, 
but  that  it  is  the  cause  of  all  cases  of  simple  jaundice 
still  lacks  proof;  a  difficulty  not  likely  to  be  overcome 
soon,  as  opportunity  for  examination  after  death  is  so 
rare. 

Another  explanation  of  simple  jaundice  has  been  set 
forth  by  Glax.  The  jaundice  arises  from  changes  in 
the  circulation  of  the  liver.  These  changes  are  due  to 
the  atony  of  the  walls  of  the  stomach  and  intestines, 
which  so  often  show  disorder  in  simple  jaundice.  If 
the  tone  of  the  walls  of  the  stomach  and  intestine  be 
decreased,  the  rapidity  of  the  blood  stream  in  the  por- 
tal vein  is  decreased.  This  being  the  case,  should  any 
increase  in  the  arterial  pulsations  appear,  the  ramifica- 
tions of  the  hepatic  artery,  the  portal  vein,  and  the 
ducts  in  the  liver  will  be  pressed  together ;  something 
must  give  way,  and  so  the  ducts  which  offer  the  least 
resistance  suffer ;  the  bile  therefore  pas5:es  into  the 
central  vein  of  the  hepatic  lobule. f 

This  theory  would  become  more  interesting  if  there 
were  any  evidence  of  the  decrease  of  the  rapidity  of 
the  stream  in  the  portal  vein.  It  would  seem,  however, 
probable,  that  if  there  be  a  catarrh  of  the  stomach  and 

*  Virchow,  Arch.  f.  path.  Anat.  1865,  Bd.  xxxii.  p.  117. 

f  Glax,  Virchow  and  Hirsch's  Jahrcsh.  f.  1875,  Bd.  ii.  p.  235.     Abstract  from 
Silz.-Dcr.dcs  Vcrcins  dcr  Acrztc  in  Stcicrinarii,  1873-74. 


Diagnosis  of  Simple  Jaundice.  401 

intestines,  there  would  be  a  greater  flow  of  blood  to 
them  ;  and  that  the  current  in  the  portal  vein  would 
not  be  thereby  decreased  in  rapidity.  If,  however,  it 
can  be  shown  that  there  is  a  decrease  in  the  pressure 
of  the  blood  in  the  vessels  of  the  liver,  I  do  not  see  any 
objection  to  the  adoption  of  Frerichs'  theory,*  of  which, 
however,  Glax  does  not  seem  willing  to  avail  himself. 

Diagnosis.  This  is  often  a  matter  of  some  difficulty, 
and  may  be  only  cleared  up  by  the  recovery  of  the 
patient,  when  it  becomes  plain  that  the  jaundice  was 
simple. 

Disease  of  other  organs  should  be  carefully  excluded, 
especially  of  the  heart  and  lungs.  I  have  known  the 
jaundice  of  nutmeg  liver  mistaken  for  a  simple  jaun- 
dice. Then  the  liver  itself  must  be  carefully  examined, 
and  if  possible  the  state  of  the  gall-bladder  made  out. 
Should  this  be  found  distended,  and  the  liver  not 
greatly  enlarged,  a  certain  advance  is  made  in  the 
diagnosis,  and  then  if  the  patient  be  young  and  for- 
merly in  good  health,  and  the  gastric  symptoms  and 
freedom  from  pain  well  marked,  the  diagnosis  may, 
with  some  likelihood,  be  made  of  simple  jaundice. 

The  absence  of  pain  is  the  great  distinguishing 
feature  in  a  diagnosis  between  simple  jaundice  and 
gall-stones.  The  liver  in  gall-stones  is  also  much 
greater  in  size,  the  jaundice  sets  in  after  an  attack  of 
pain,  and  the  staining  of  the  skin  and  urine  is  much 
deeper.  Simple  jaundice  shows  little  besides  the 
staining  of  the  tissues  and  the  gastric  symptoms. 

Prognosis.  If  the  diagnosis  can  be  safely  made,  the 
prognosis  becomes  exceedingly  good.  But  even  in  the 
mildest  case,  the  mind  of  the  practitioner  cannot  be 
quite  easy  ;  for  it  is  these  apparently  typical  cases  of 
simple  jaundice  that   now  and  then    develope  all    the 

*  Frerichs,  op.  cit.  Bd.  i.  p.  8g. 

DD 


402  Treatment  of  Simple  Jaundice. 

symptoms  oi  icterus  gravis.'^  Until  the  grave  symptoms 
come  on  there  is  no  means  whatever  of  distinguishing 
between  ordinary  simple  jaundice  and  the  jaundice 
which  is  the  forerunner  of  icterus  gravis.  The  line 
which  separates  these  two  must  be  very  narrow.  The 
same  poison,  such  as  a  foul  smell,  which  gives  to  one 
person  a  gastric  or  intestinal  catarrh  with  jaundice, 
seems  to  lead  in  another  to  the  same  disorder,  but  with 
the  addition  of  parenchymatous  degenerations  in  all  the 
glands  and  muscles,  as  well  as  of  the  stomach.  It 
seems  to  be  a  question  of  degree,  not  of  kind. 

Treatment.  It  would  be  unwise  to  treat  actively  a 
disease  which  naturally  ends  in  recovery.  The  treat- 
ment must  therefore  be  limited  to  that  which  will  cer- 
tainly do  no  harm,  and  it  will  be  profitable  to  keep  the 
gastric  symptoms  only  in  view  and  to  treat  them.  It  is 
most  important  to  avoid  all  means  that  may  aggravate 
the  state  of  the  patient.  For  instance,  a  mercurial 
purge  may  be  given  at  the  onset  of  the  disorder,  if  such 
be  indicated  by  the  sluggishness  of  the  patient's  bowels. 
But  the  repetition  of  this  dose,  or  the  daily  administra- 
tion of  mercury,  such  as  now  and  then  may  be  heard 
of,  is  a  serious  damage  to  the  patient.  The  same  may 
be  said  of  antimony,  chloral,  or  any  other  drug  which 
causes  a  parenchymatous  degeneration  of  organs.  For 
it  will  be  impossible  to  tell  how  far  from,  or  how  near 
to,  the  border  line  that  separates  icterus  gravis  from 
simple  jaundice  the  patient  is,  and  the  introduction  of 
such  a  body  as  mercury  into  the  oeconomy  may  deter- 
mine the  arrival  of  the  graver  symptoms. 

The  best  plan  of  treatment  would  seem  to  be  to  be- 
gin with  a  purgative,  if  the  patient's  bowels  should  not 

*  Icteii  nunquam  spernendi,  nam  sub  larva  ac  persona  icteri  saepe  magni,  peri- 
culosi,  ac  repenlini  morbi  absconduntur ;  et  sacpissime  moriuntur  derepente 
icterici,  ut  ait  Dodonaeus.  (Stoll,  Aphorism,  in  Rat.  Med.  Vienna^,  1790,  Pars  vi. 
Sect.  i.  §  103.  p.  29.) 


Treatment  of  Simple  Jaundice.  403 

be  already  too  much  open.  The  purgatives  may  be  vege- 
table ;  the  compound  colocynth  pill  of  the  pharmaco- 
poeia; or  to  which  a  few  grains  of  calomel  may  be  added. 
Alkalies  may  then  be  administered,  with  bismuth,  be- 
fore food.  The  diet  should  be  strictly  regulated.  All 
indigestible  matters,  as  vegetables  and  fruit,  must  be 
forbidden  ;  and  the  diet  restricted  to  milk,  soups,  with- 
out vegetables,  or  in  which  vegetables  have  been  boiled, 
and  then  strained  out,  and  some  small  amount  of 
farinaceous  food.  Coffee,  tea,  and  alcohol  must  be 
forbidden.  The  patient  may  be  allowed  acid  drinks, 
such  as  lemonade.  As  the  gastric  symptoms  subside, 
white  fish  and  then  meat  may  be  allowed,  and  the  alka- 
line treatment  may  be  changed  to  a  course  of  aqua 
regia. 

Emetics  have  long  been  a  favourite  remedy,  and  Sir 
Dominic  Corrigan  specially  praises  ipecacuan,  by  the 
action  of  which  he  thinks  he  has  warded  off  the  onset 
of  the  graver  symptoms,  and  even  cured  a  case  of  acute 
yellow  atrophy.*  I  must  own  that  ipecacuan,  still 
more  tartar  emetic,  appear  to  me  dangerous  remedies; 
for  the  diagnosis  must  be  indeed  certain  before  emetics 
can  be  given  with  confidence.  They  are  supposed  to 
act  by  compression  of  the  gall-bladder  and  forcible  ex- 
pulsion of  its  contents  into  the  duodenum.  The  serious 
results  of  violent  efforts  at  vomiting,  if  a  wrong  diagno- 
sis should  chance  to  have  been  made,  need  scarcely  be 
pointed  out ;  if  the  ducts  be  obstructed  by  a  gall-stone,  or 
the  head  of  the  pancreas  enlarged,  vomiting  seems 
more  likely  to  be  followed  by  a  rupture  of  the  bile  pas- 
sages behind  the  stone  than  by  any  good  to  the  patient. 
Again,  as  Bamberger  has  quite  correctly  pointed  out,f 
jaundice  is  not  an  unknown  sequence  of  the  administra- 
tion of  emetics  themselves. 

*  Corrigan,  Dublin  Hasp.  Gaz.  1845,  pp.  69  and  71. 
f  Bamberger,  op.  cit.  p.  568. 

DD  2 


404  Treatment  of  Simple  Jaundice. 

The  same  cautions  must  be  applied  to  another 
method  of  treatment  which  Gerhardt  has  of  late  in- 
troduced, pressure  and  faradization  of  the  gall-bladder. 
The  employment  of  electricity  is  indeed  not  new,  as 
Erasmus  Darwin  says  that  he  gave  half-a-score  of 
smart  electric  shocks  along  the  course  of  the  bile  ducts 
from  a  coated  bottle  to  a  man  who  had  been  jaundiced 
for  six  weeks,  and  the  same  day  the  stools  became 
yellow.* 

Gerhardt  grasps  the  enlarged  gall-bladder  with  his 
fingers,  and  endeavours  to  squeeze  its  contents  out. 
He  says  that  the  gall-bladder  may  be  felt  gradually 
emptying  itself,  and  a  sort  of  fremitus  appears  to  accom- 
pany it.  After  this,  the  gall-bladder  can  no  longer  be 
made  out  by  percussion,  and  on  the  second  day  the 
faeces  become  coloured.  Gerhardt  also  places  one 
electrode  over  the  gall-bladder,  the  other  on  the  spine 
at  a  level  with  the  first,  and  then  passes  strong  induc- 
tion currents  between  the  two ;  after  three  or  four  days 
the  stools  become  coloured. f 

For  my  own  part  I  should  scarcely  like  to  adopt  such 
active  measures.  It  would  be  altogether  different  if  the 
advantage  to  the  patient  were  to  be  great,  as  the  taxis 
in  hernia ;  but  the  disease  here  is  a  very  mild  one,  and 
th^  remedy  may  possibly  prove  worse  than  the  disease. 
I  do  not  think  that  it  is  justifiable  to  expose  the  patient 
to  the  risk  of  rupturing  the  ducts  or  the  gall-bladder  ; 
and  if  the  theory  of  jaundice  from  catarrh  of  the  stomach 
and  duodenum  be  allowed,  the  primary  disease  would 
not  be  overcome  by  the  ejection  of  the  plug  of  mucus 
into  the  duodenum,  but  it  is  probable  that  the  plug 
would  be  renewed,  the  catarrh  remaining,  as  soon  as 
the  excess  of  bile  had  passed  through  the  papilla.    In- 

*  Erasmus  Danvin,  Zoonomia,  §  xxx.  Lond.  1801.  3rd  Ed.  Vol.  ii.  p.  2. 
f  Gerhardt,   Ueber  Ictertis  gastro-ditodcnalis,  in  Volkmann's   Sammlung   klin. 
Vortrdge  {Innerc  Medicin,)  Leipzig,  1870-75,  p.  112. 


Treatment  of  Simple  Jaundice.  405 

deed,  the   passage   of  the  bile  over  the  mucous  mem- 
brane is  not  Hkely  to  aid  its  recovery. 

Krull  recommends  the  daily  injection  of  cold  water  into 
the  rectum .  He  says  it  has  been  so  successful  that  he  has 
never  had  to  repeat  it  more  than  seven  times.  One  or 
two  litres  (from  two  to  four  pints)  of  a  temperature  of 
60°  F.  (15°  C.)  are  thrown  up  the  bowel,  and  allowed  to 
be  retained  as  long  as  possible.  The  temperature  of 
the  water  must  be  gradually  raised  with  each  successive 
injection.* 

*  Krull,  Berlin,  kiln.  Woch.  1877,  p.  159. 


MEDICAL    WORKS, 


PUBLISHED    BT 


JD.    APPLETON   &    COMPANY, 

549  &  551    Broadway,   New  York. 


FBICB 


ANSTIE  (FRANCIS  E.)  Neuralgia,  and  Diseases  which  resemhle  it. 
By  Francis  E.  Anstie,  M.  D.,  F.  R.  C.  P.,  Senior  Assistant  Physician 
to  Westminster  Hospital ;  Lecturer  on  Materia  Medica  in  West- 
minster Hospital  School ;  and  Physician  to  the  Belgrave  Hospital 
for  Children  ;  editor  of  "  The  Practitioner  "  (London),  etc.  1  vol., 
12mo Cloth,  $2  50* 

BARKER  (FORDYOE).  On  Sea-Sickness.  A  Popular  Treatise  for 
Travelers  and  the  General  Reader.  By  Fordyce  Barker,  M.  D., 
Clinical  Professor  of  Midwifery  and  Diseases  of  Women  in  the 
Bellevue  Hospital  Medical  College,  etc.     Small  12mo Cloth,         75 

On  Puerperal  Disease.     Clinical  Lectures  delivered  at  Bellevue 

Hospital.     A  Course  of  Lectures  valuable  alike  to  the  Student  and 

the  Practitioner.     Third  edition.     In  1  vol.,  8vo Cloth,     5  00* 

Sheep,     6  00* 

BARNES  (ROBERT).  Lectures  on  Obstetric  Operations,  including  the 
Treatment  of  Hsemorriiage,  and  forming  a  Guide  to  the  Manage- 
ment of  Difficult  Labor.  By  Robert  Barnes,  M.  D.,  F.  R.  C.P., 
Fellow  and  late  Examiner  in  Midwifery  at  the  Royal  College  of 
Physicians;  Examiner  in  Midwifery  at  the  Royal  College  of  Sur- 
geons, London,  1  vol.,  8vo.  Third  edition,  revised  and  extended. 
Illustrated Cloth,     4  50* 

BARTHOLOW'S  Treatise  on  Materia  Medica  and  Therapeutics.  A  new 
and  revised  edition.  By  Roberts  Bartholow,  M.  A..  M.  D.,  Profes- 
sor of  Materia  Medica  and  Therapeutics  in  the  Jefferson  Medical 
College;  late  Professor  of  the  Theory  and  Practice  of  Medicine,  and 
of  Clinical  Medicine,  and  formerly  Professor  of  Materia  Medica  and 
Therapeutics,  in  the  Medical  College  of  Ohio.  Revised  edition  of 
1879.     1  vol.,  8vo.     548  pages Cloth,  $5.00 ;  Sheep,     6  00* 

Practice  of  Medicine {In  press.) 

BASTIAN  (H.  CHARLTON,  M.  D.,  F.  R.  S.)  On  Paralysis  from  Brain- 
Disease  in  its  Common  Forms.     1  vol.,  12mo Cloth,     1  75 

Diseases  of  Nerves  and  Spinal  Cord. .  .{In press.) 

BENNET  (J.  H.)  Winter  and  Spring  on  the  Shores  of  the  Mediterra- 
nean; or.  The  Riviera,  Mentone,  Italy,  Corsica,  Sicily,  Algeria, 
Spain,  and  Biarritz,  as  Winter  Climates.  By  J.  Henry  Bennet, 
M.  D.,  Member  of  the  Royal  College  of  Physicians,  London.  With 
numerous  Illustrations.    1  vol.,  12mo.    New  revised  edition .  Cloth,     3  50* 

On  the  Treatment  of  Pulmonary  Consumption,  by  Hygiene, 

Climate,  and  Medicine.     1  vol.,  thin  8vo Cloth,     1  50* 


FRIOX 

BILLKOTH  (Dr.  THEODOR).  General  Surgical  Pathology  and  Thera- 
peutics. A  Text-hook  for  Students  and  Physicians.  By  Dr.  Theo- 
dor  Billroth,  Professor  of  Surgery  in  Vienna.  From  the  eighth  . 
German  edition,  hy  special  permission  of  the  author,  hy  Charles  E. 
Ilackley,  M.  D.,  Surgeon  to  the  New  York  Eye  and  Ear  Infirmary; 
Physician  to  the  New  York  Hospital.  Fonrth  American  edition,  rcYised 
and  enlarged.     1  vol.,  8vo Cloth,  $5.00* ;  Sheep,  $6  00* 

BTJCK  (GURDON).  Contributions  to  Reparative  Surgery,  showing  its 
Application  to  the  Treatment  of  Deformities,  produced  by  Destruc- 
tive Disease  or  Injury ;  Congenital  Defects  from  Arrest  or  Excess 
of  Development ;  and  Cicatricial  Contractions  following  Burns. 
Illustrated  hy  Thirty  Cases  and  fine  Engravings.    1  vol.,  8vo.  .Cloth,     3  00* 

CARPENTER  (W.  B.)  Principles  of  Mental  Physiology,  with  their 
Application  to  the  Training  and  Discipline  of  the  Mind,  and  the 
Study  of  its  Morbid  Conditions.  By  "William  B.  Carpenter,  M.  D., 
LL.  D.,  F.  R.  S.,  F.  L.  S.,  F.  G.  S.,  Registrar  of  the  University  of 
London,  etc.     1  vol.,  12mo ; . .  .Cloth,     3  00 

CHAUVEAU.  The  Comparative  Anatomy  of  Domesticated  Animals. 
By  A.  Chauveau,  Professor  at  the  Lyons  Veterinary  School.  Sec- 
ond edition,  revised  and  enlarged,  with  the  Cooperation  of  S. 
Arlong,  Professor  at  the  Toulouse  Veterinary  School.  Translated 
and  edited  by  George  Fleming,  F.  R.  G.  S.,  M.  A.  I.,  etc.  With  450 
Illustrations.     1  vol.,  8vo Cloth,     6  00 

COMBE  (ANDREW).  The  Management  of  Infancy,  Physiological  and 
Moral.  By  Andrew  Comhe,  M.  D.  Revised  and  edited  by  Sir  James 
Clark,  Bart.,  K.  C.  B.,  M.  D.,  F.  R.  S.     1  vol.,  12mo Cloth,     1  50 

DAVIS  (HENRY  G.)     Conservative  Surgery.     With  Illustrations.     1 

vol.,  8vo Cloth,     3  00* 

ECKER    (ALEXANDER).      Convolutions  of  the   Brain.      Translated 

from  the  German  by  Robert  T.  Edes,  M.  D.     1  vol.,  8vo Cloth,     1  25* 

ELLIOT  (GEORGE  T.)  Obstetric  Clinic :  A  Practical  Contrihution  to 
the  Study  of  Obstetrics,  and  the  Diseases  of  Women  and  Children. 
By  George  T.  Elliot,  Jr.,  A.  M.,  M.  D.     1  vol.,  8vo Cloth,     4  50* 

FLINT'S  Manual  of  Chemical  Examinations  of  the  Urine  in  Disease; 
with  Brief  Directions  for  the  Examination  of  the  most  Common 
Varieties  of  Urinary  Calculi.     By  Austin  Flint,  Jr.,  M.  D.     1  vol. 

Revised  edition Cloth,     1  00* 

Physiology  of  Man.     Designed  to  represent  the  Existing  State  of 

Physiological  Science  as  applied  to  the  Functions  of  the  Human 
Body.  By  Austin  Flint,  Jr.,  M.  D.,  Professor  of  Physiology  and 
Microscopy  in  the  Bellevue  Hospital  Medical  College,  New  York ; 
Fellow  of  the  New  York  Academy  of  Medicine ;  Member  of  the 
Medical  Society  of  the  County  of  New  York;  Resident  Member 
of  the  Lyceum  of  Natural  History  in  the  City  of  New  Yoi-k,  etc. 
Complete  in  5  vols. 
Vol.  1.  Introduction;  The  Blood;  Circulation;  Respiration.  8vo. 
Vol.  2.  Alimentation  ;     Digestion  ;     Absorption  ;     Lymph,    and 

Chyle.     8vo. 
Vol.3.  Secretion;  Excretion;  Ductless  Glands;  Nutrition;  Ani- 
mal Heat;  Movements;  Voice  and  Speech.    1  vol.,  8vo. 
Vol.  4.  The  Nervous  System.     1  vol.,  8vo. 
Vol.  5.  (With  a  General  Index  to  the  five  volumes.)  Special  Senses; 

Generation.     Per  vol Cloth,  $4.50* ;  Sheep,     5  60* 

The  five  volumes Cloth,  $22.00*;  Sheep,  27  00* 


PBIOB 

FLINT'S  Text-Book  of  Human  Physiology;  designed  for  the  Use  of 
Practitioners  and  Students  of  Medicine.  Illustrated  by  three  Litho- 
graphic I'lates,  and  three  hundred  and  thirteen  Woodcuts.  Second 
edition,  revised.     1  vol.,  imperial  8vo Cloth,  $0.00*  ;  Sheep,  |7  00* 

The  Physiological  Effects  of  Severe  and  Protracted  Muscular  Ex- 
ercise; with  Special  Reference  to  its  Influence  upon  the  Excretion 
of  Nitrogen.     By  Austin  Flint,  Jr.,  M.D.,  etc.    1  vol.,  12rao. Cloth,     1  00 

The  Source  of  Muscular  Power.    Arguments  and    . 

Conclusions  drawn  from  Observation  upon  the  Human  Subject  un- 
der Conditions  of  Rest  and  of  Muscular  Exercise 1  00* 

FREY  (HEINRICH).  The  Histology  and  Histochemistry  of  Man.  A 
Treatise  on  the  Elements  of  Composition  and  Structure  of  the  Human 
Body.  By  Heitirich  Frey,  Professor  of  Medicine  in  Zurich.  Trans- 
lated from  the  fourth  German  edition,  by  Arthur  E.  J.  Barker,  Sur- 
geon to  the  City  of  Dublin  Hospital;  Demonstrator  of  Anatomy, 
Royal  College  of  Surgeons,  Ireland;  Visiting  Surgeon,  Convalescent 
Home,  Stillorgan  ;  and  revised  by  the  author.  With  008  Engravings 
on  Wood.     1  vol.,  Svo Cloth,  $5.00*  ;  Sheep,     6  00* 

HAMILTON  (ALLAN  MoL.,  M.  D.)  Clinical  Electro-Therapeutics, 
Medical  and  Surgical.  A  Hand-Book  for  Physicians  in  the  Treat- 
ment of  Nervous  and  other  Diseases.     1  vol.,  Svo Cloth,     2  00* 

HAMMOND  (W.  A.)  A  Treatise  on  Diseases  of  the  Nervous  System. 
By  William  A.  Hammond,  M.  D.,  Professor  of  Diseases  of  the  Ner- 
vous System  and  of  Clinical  Medicine  in  the  Bellevue  Hospital  Medi- 
cal College  ;  Physician-in-Chief  to  the  New  York  State  Hospital  for 
Diseases  of  the  Nervous  System,  etc.  New  edition,  with  109  Illus- 
trations.    Rewritten,  enlarged,  and  improved.     1  vol.,  large  Svo. 

Cloth,  $6.00* ;  Sheep,     7  00* 

Clinical  Lectures  on  Diseases  of  the  Nervous  System.    Delivered 

at  Bellevue  Hospital  Medical  College.     Edited  by  T.  M.  B.  Cross, 

M.  D.     1  vol.,  Svo Cloth,     3  50* 

HEALTH  PRIMERS.  Edited  by  J.  Langdon  Down,  M.  D.,  F.  R.  C.  P. ; 
Henry  Power,  M.  B.,  F.  R,  C.  S. :  J.  Mortimer-Granville,  M.  D.,  and 

John  Tweedy,  F.  R.  C.  S.     Square  Ifimo Cloth,  each        40 

Now  Beady: 


L  Exercise  and  Training. 
II.  Alcohol :  Its  Use  and  Abuse. 
III.  Premature  Death :    Its  Promo- 
tion or  Prevention. 


IV.  The  House  and  its  Surroundings. 
V.  Personal  Appearance  in  Health 

and  Disease. 
VI.  Baths  and  Bathing. 


HOFFMANN-ULTZMANN.  Introduction  to  an  Investigation  of  Urine, 
with  Special  Reference  to  Diseases  of  the  Urinary  Apparatus.  By 
M.  B.  Hoffmann,  Professor  in  the  University  of  Gratz,  and  R.  Ultz- 
mann,  Tutor  in  the  University  of  Vienna.  Second  enlarged  and 
improved  edition _^ (In  press.) 

HOFFMANN  (FREDERICK,  Ph.D.,  Pharmaceutist  in  New  York). 
Manual  of  Chemical  Analysis,  as  applied  to  the  Examination  of 
Medicinal  Chemicals.  A  Guide  for  the  Determination  of  their  Iden- 
tity and  Quality,  and  for  the  Detection  of  Impurities  and  Adultera- 
tions. For  the  Use  of  Pharmaceutists,  Physicians,  Druggists,  and 
Manufacturing  Chemists  and  Students^ Cloth,     3  00* 

HOLLAND  (Sir  HENRY).     Recollections  of  Past  Life.    Reminiscences 

of  Men,  Manners,  and  Things.    1  vol.,  12mo Cloth,     2  00 


PBioa 
HOWE  (JOSEPH  W.)     Emergencies,  and  How  to  Treat  Them.     Bj 
Joseph  W.  Howe,  M.  D.,  Visiting  Surgeon  to  Charity  Hospital ; 
Clinical  Professor  of  Surgery  in  the  Medical   Department  of  the 
University  of  New  York,  etc.     1  vol.,  8vo Cloth,  $2  50* 

The  Breath,  and  the  Diseases  which  give  it  a  Fetid  Odor.     With 

Directions  for  Treatment.     1  vol.,  12mo Cloth,     1  00 

HUXLEY.     The  Anatomy  of  Vertebrated  Animals.    By  Thomas  Henry 

Huxley,  LL.  D.,  F.  Pv.  S.     1  vol.,  12mo Cloth,     2  50 

The  Anatomy  of  Invertebrated  Animals.     By  Thomas  Henry 

Huxley,  LL.  D.,  F.  E.  S.     1  vol.,  12mo Cloth,     2  50 

HUXLEY  and  YOUMANS'S  Elements  of  Physiology  and  Hygiene.    By 

T.  Huxley  and  W.  J.  Youmans.     1  vol.,  12mo Cloth,     1  50 

JOHNSTON'S  Chemistry  of  Common  Life.     2  vols.,  12mo Cloth,     3  00 

KEYES.  The  Tonic  Treatment  of  Syphilis,  including  Local  Treatment 
of  Lesions.  By  E.  L.  Keyes,  Adjunct  Professor  of  Surgery,  and 
Professor  of  Dermatology,  BeUevue  Hospital  Medical  College,  and 
Surgeon  to  Bellevue  Hospital.     1  vol.,  8vo Cloth,     1  00* 

LETTERMAN  (J.,  M.  D.)     Medical  Eecollections  of  the  Army  of  the 

Potomac.     1  vol.,  8vo Cloth,     1  00 

LEWES'S  Physiology  of  Common  Life.     2  vols.,  12mo Cloth,     3  00 

MARKOE  (T.  M.)  A  Treatise  on  Diseases  of  the  Bones.  By  Thomas 
M.  Markoe,  M.  D.,  Professor  of  Surgery  in  the  College  of  Physicians 
and  Sui-geons.     With  Illustrations.     1  vol.,  Svo Cloth,     4  50* 

MAUDSLEY  (HENRY).  Body  and  Mind :  an  Inquiry  into  their  Con- 
nection and  Mutual  Influence,  specially  in  reference  to  Mental 
Disorders.  An  enlarged  and  revised  edition,  to  which  are  added 
Psychological  Essays.  By  Henry  Maudsley,  M.  D.,  London,  Fellow 
of  the  Roval  College  of  Physicians  ;  Professor  of  Medical  Jurispru- 
dence in  Universify  College,  London,  etc.     1  vol.,  12nio Cloth,     1  50 

Pliysiology  of  the  Mind.     Vol.  I.    Being  the  first  part  of  a  third 

edition,  revised,  enlarged,   and  in  great  part  rewritten,  of  "  The 
Physiology  and  Pathology  of  the  Mind."     1  vol.,  12mo Cloth,     2  00 

Responsibility  in  Mental  Disease.  (International  Scientific  Series.) 

1  vol.,  12mo Cloth,     1  50 

MoSHERRY.  Health,  and  How  to  Promote  It.  By  Richard  McSherry, 
M.  D.,  Professor  of  Practice  of  Medicine,  University  of  Maryland ; 
President  of  Baltimore  Academy  of  Medicine.   1  vol.,  12mo.  .Cloth,     1  25 

MEYER  (Dr.  MORITZ).  Electricity  in  its  Relations  to  Practical  Medi- 
cine. Translated  from  the  third  German  edition,  with  numerous 
Notes  and  Additions,  by  William  A.  Hammond,  M.  D.,  Professor  of 
Diseases  of  the  Mind  and  Nervous  System,  in  the  Bellevue  Hospital 
Medical  College,  etc.      With  numerous  Illustrations.      1  vol.,  Svo. 

Cloth,     4  60* 

NEFTEL  (WM.  B.,  M.  D.)  Galvano-Therapeutics.  The  Physiological 
and  Therapeutical  Action  of  the  Galvanic  Current  upon  the  Acoustic, 
Optic,  Sympathetic,  and  Pneumogastric  Nerves.     12mo Cioth,     1  50* 

NEUMANN  (ISIDOR).  lland-Book  of  Skin  Diseases.  By  Dr.  Isidor 
Neumann.  Tnnslated  by  Lucius  D.  Bulkley,  A.  M..  M.  D.  Illus- 
trated with  60  Wood  Engravings.  1  vol.,  Svo.  .Cloth,  $4.00*;  Sheep,     5  00* 


5 

PRIOB 

NEW  YORK  MEDICAI.  JOURNAL.  Edited  by  James  B.  Hunter,  M.  I). 

The  largest  raedical  monthly  published Terms  per  annum,  $4  00* 

Specimen  numbers  sent  by  mail  on  receipt  of  25  cents. 

NIEMEYER  (Dr.  FELIX  VON).  A  Text-Book  of  Practical  Medicine, 
with  Particular  Reference  to  Physiology  and  Pathological  Anatomy. 
Containing  all  the  author's  Additions  and  Revisions  in  the  eighth 
and  last  German  edition.  Translated  from  the  German  edition,  by 
Georye  H.  Humphreys,  M.  D.,  and  Charles  E.  Haekley,  M.  D.  2 
vols.,  8vo Cloth,  $9.00*  ;  Sheep,  $11  00* 

NIGHTINGALE'S  (FLORENCE)  Notes  on  Nursing.     What  it  is,  and 

what  it  is  not.     1  vol.,  12mo Cloth,        75 

PAGET.  Clinical  Lectures  and  Essays.  By  Sir  James  Paget,  Bart., 
F.  R.  S.,  D.  C.  L.,  Oxon.,  LL.  D.,  Cantab,  etc.  Edited  by  Howard 
Marsh,  F.  R.  C.  S.,  etc.     1  vol.,  8vo Cloth,     5  00* 

PEASLEE  (E.  R.)  A  Treatise  on  Ovarian  Tumors;  their  Pathology, 
Diagnosis,  and  Treatment,  with  Reference  especially  to  Ovariotomy. 
By  E.  R.  Peaslee,  M.  D.,  LL.  D.,  Professor  of  Diseases  of  "Women, 
in  Dartmouth  College;  one  of  the  Consulting  Surgeons  to  the  New 
York  State  Woman's  Hospital;  formerly  Professor  of  Obstetrics 
and  Diseases  of  Women,  in  the  New  York  Medical  College ;  Corre- 
sponding Member  of  the  Obstetrical  Society  of  Berlin,  etc.  In  one 
large  vol.,  8vo.     With  Illustrations Cloth,  $5.00* ;  Sheep,     6  00* 

PEREIRA'S  (Dr.)  Elements  of  Materia  Medica  and  Therapeutics. 
Abridged  and  adapted  for  the  Use  of  Medical  and  Pharmaceutical 
Practitioners  and  Students,  and  comprising  all  the  iledicines  of  the 
British  Pharmacopoeia,  with  such  others  as  are  frequently  ordered 
in  Prescriptions,  or  required  by  the  Physician.  Edited  by  Robert 
Bentley  and  Theophilus  Redwood.    New  edition.    1  vol.,  royal  Svo. 

Cloth,  $7.00* ;  Sheep,     8  00* 

REPORTS.  Bellevue  and  Charity  Hospital  Reports  for  1870.  Containing 
Valuable  Contributions  from  Isaac  E.  Taylor,  M.  D.,  Austin  Flint, 
M.D.,  Lewis  A.  Sayre,  M.  D.,  W.  A.  Hammond,  M.  D.,  T.  Gaillard 
Thomas,  M.  D.,  Frank  H.  Hamilton,  M.  D.,  and  others.    1  vol.,  8vo. 

Cloth,     4  00* 

RICHARDSON.  Diseases  of  Modern  Life.  By  Benjamin  Ward  Rich- 
ardson, M.  D.,  M.  A.,  F.  R.  S.,  Fellow  of  the  Royal  College  of  Phy- 
sicians.    1  vol.,  12mo Cloth,     2  00 

ROSCOE  and  SCHORLEMMER.  A  Treatise  on  Chemistry  by  H.  E. 
Roscoe,  F.  R.  S.,  and  C.  Schorlemmer,  F.  R.  S.,  Professors  of  Chem- 
istry in  Owens  College,  Manchester.  To  be  completed  in  three  vol- 
umes.    Fully  illustrated. 

N'aw  Beady: 

Vol.  I.  The  Non-metallic  Elements.     Svo Cloth,     5  00 

Vol.  II.,  Part  I.  Metals.     8vo Cloth,     3  00 

In  Preparatiot^ : 
Vol.  II.,  Part  II.  Metals. 

SAYRE  (LEWIS  A.,  M.  D.)  Practical  Manual  of  the  Treatment  of 
Club-Foot.  By  Lewis  A.  Sayre,  M.  D.,  Professor  of  Orthopedic 
Surgery  in  the  Bellevue  Hospital  Medical  College;  Surgeon  to 
Bellevue  Hospital,  etc.     New  edition.     1  vol.,  12mo Cloth,     1  25* 

Lectures  on  Orthopedic  Surgery  and  Diseases  of  the  Joints,  de- 
livered at  Bellevue  Hospital  Medical  College  during  the  Winter  Ses- 
sion of  1874^'75,  by  Lewis  A.  Sayre,  M.  D  . . .  Cloth,  $5.00* ;  Sheep,     6  00* 


6 

PRICE 

SCHEOEDER  (Dr.  ElA-RL).  A  Manual  of  Midwifery,  including  the 
Pathology  of  Pregnancy  and  the  Puerperal  State.  By  Dr.  Karl 
Schroeder,  Professor  of  Midwifery,  and  Director  of  the  Lying-in  In- 
stitution, in  the  University  of  Erlangen.  Translated  into  English  from 
the  third  German  edition,  by  Charles  H.  Carter,  B.  A.,  M.  D.,  B.  S., 
London  ;  Member  of  the  Royal  College  of  Physicians,  London,  etc. 
With  26  Engravings  on  Wood.     1  vol.,  8vo..  .Cloth,  $3.50*;  Sheep,  $4  50* 

SBIPSON  (Sir  JAMES  Y.)  Selected  Obstetrical  and  Gynecological 
Works  of  Sir  James  Y.  Simpson,  Bart.,  M.  D.,  and  late  Professor 
of  Midwifery  in  the  University  of  Edinburgh.  Edited  by  J.  Watt 
Black,  M.  A.,  M.  D.,  M.  R.  C.  P.  L. ;  Physician  Accoucheur  to  Cljar- 
ing  Cross  Hospital,  London,  and  Lecturer  on  Midwifery  and  the 
Diseases  of  Women  and  Children  in  the  Hospital  School  of  Medi- 
cine.    1  vol.,  8vo Cloth,  $.3.00*  ;  Sheep,     4  00* 

Anaesthesia,  Hospitalism,  etc.     By  Sir  James  Y.  Simpson,  Bart., 

M.  D.     Edited  by  Sir  Walter  Simpson,  Bart.  .Cloth,  $3.00*;  Sheep,     4  00* 

SIMPSON  (Sir  JAMES  Y.)  The  Diseases  of  Women.  By  Sir  James  Y. 
Simpson,  Bart.,  M.  D.  Edited  by  Alexander  Simpson,  M.  D.,  Pro- 
fessor of  Midwifery  in  the  University  of  Edinburgh. 

Cloth,  $3.00*;  Sheep,     4  00 

SMITH  (EDWARD,  M.  D.,  LL.  B.,  F.  R.  S.)  Foods.  (International  Sci- 
entific Series.) 1  75 

Health:  A Hand-Book  for  Households  and  Schools.  12mo.  .Cloth,     1  00 

STEIKER.  Compendium  of  Children's  Diseases:  A  Hand-Book  for 
Practitioners  and  Students.  By  Dr.  Johannes  Steiner,  Professor  of 
Diseases  of  Children  in  the  University  of  Prague,  etc.  Translated 
from  the  second  German  edition,  by  Lamson  Tait,  F.  R.  C.  S.,  etc. 
1  vol.,  8vo Cloth,  $3.50* ;  Sheep,     4  50* 

STROUD  (WILLIAM,  M.D.)  The  Physical  Cause  of  the  Death  of 
Christ,  and  its  Relations  to  the  Principles  and  Practice  of  Christian- 
ity. With  Letter  on  the  Subject  by  Sir  James  Y.  Simpson,  Bart., 
M.D.    12mo Cloth,     2  00 

BWETT.  A  Treatise  on  the  Diseases  of  the  Chest.  Being  a  Course  of 
Lectures  delivered  at  the  New  York  Hospital.  By  John  A.  Swett, 
M.D.     1  vol.,  Svo Cloth,     3  50* 

TILT'S  Hand-Book  of  Uterine  Therapeutics.    Second  American  edition, 

revised  and  amended.     1  vol.,  Svo,  368  pages Cloth,     3  50* 

VAN  BUREN  (W.  H.)  Lectures  upon  Diseases  of  the  Rectum,  deliv- 
ered at  the  Bellevue  Hospital  Medical  College,  Session  1869-1870, 
by  W.  H.  Van  Buren,  A.  M.,  M.  D.,  Professor  of  the  Principles  of 
Surgery,  with  Diseases  of  the  Genito-Urinary  Organs,  etc.,  in  the 
Bellevue  Hospital  Medical  College ;  one  of  the  Consulting  Surgeons 
of  the  New  If  oi-k  IIo.spital,  of  the  Bellevue  Hospital ;  Member  of 
the  New  York  Academy  of  Medicine,  of  the  Pathological  Society 
of  New  York,  etc.     1  vol.,  12mo Cloth,     1  50* 

A  Practical  Treatise  on  the  Surgical  Diseases  of  the  Genito-Uri- 
nary Organs,  including  Syphilis.  Designed  as  a  Manual  for  Students 
and  Practitioners.  With  Engravings  and  Cases.  By  W.  H.  Van 
Buren,  A.  M.,  M.  D.,  and  Edward  L.  Keyes,  A.  M.,  M.  D.,  Professor 
of  Dermatology  in  Bellevue  Hospital  Medical  College,  Surgeon  to 
the  Charity  Hospital,  Venereal  Division;  Consulting  Dermatologist 
to  the  Bureau  of  Out-Door  Relief,  Bellevue  Hospital,  etc.  1  vol., 
Svo Cloth,  $5.00* ;  Sheep,     6  00* 


pracK 


VGGEL  (A.)  A  Practical  Treatise  on  the  Diseases  of  Children.  By 
Alfred  Vogel,  M.  D.,  Professor  of  Clinical  Medicine  in  the  Uni- 
versity of  Dorpat,  Russia.  Translated  and  edited  by  H.  Raphael, 
M.  D.,  late  House  Surgeon  to  Bellevue  Hospital,  Attending  Physi- 
cian to  the  Eastern  Dispensary  for  the  Diseases  of  Children,  etc. 
From  the  fourth  German  edition.  Hlustrated  by  Six  Lithographic 
Plates.     1  vol.,  8vo Cloth,  $4.50* ;  Sheep,  $5  50* 

WAGNER  (RUDOLF).  Hand-Book  of  Chemical  Technology.  Trans- 
lated and  edited  from  the  eighth  German  edition,  with  extensive 
Additions,  by  William  Crookes,  F.  R.  S.  With  336  Illustrations.  1 
vol.,  8vo.     761  pages Cloth,     5  00* 

WALTON  (GEORGE  E.,  M.D.)  Mineral  Springs  of  the  United  States 
and  Canadas.  Containing  the  latest  Analyses,  with  full  Descrip- 
tion of  Localities,  Routes,  etc.     12mo Cloth,     2  00 

WELLS  (Dr.  T.  SPENCER).     Diseases  of  the  Ovaries.     1  vol.,  8vo. . .     4  50* 

WYLIE  (W.  GILL,  M.  D.)  Hospitals :  History  of  their  Origin,  Develop- 
ment, and  Progress,  during  the  First  Century  of  the  American  Re- 
public. Boylston  Prize-Essay  of  Harvard  University  for  1876.  1 
vol.,  8vo Cloth,     2  50* 


Appletons'   Journal. 

PUBLISHED    MONTHLY. 

The  proprietors  of  AFPiiBTONs'  Joitbwal  will  henceforth  devote  it  exclusively  to  literatare  of 
a  high  order  of  excellence,  by  writers  of  acknowledged  standing. 

It  is  the  growing  habit  of  the  leading  minds  in  all  conntries  to  contribute  their  best  intellec- 
tual work  to  the  magazines  and  reviews  ;  and,  in  order  that  Appletons'  Journal  may  adequately 
reflect  the  intellectual  activity  of  the  time  thus  expressed,  it  will  admit  to  its  pages  a  selection 
of  the  more  noteworthy,  critical,  speculative,  and  progressive  papers  that  come  from  the  pens  of 
these  writers. 

Fiction  will  still  occupy  a  place  in  the  Journal,  and  descriptive  papers  will  appear;  but  large 
place  will  be  given  to  articles  bearing  upon  literary  and  art  topics,  to  discussions  of  social  and 
political  progress,  to  papers  addressed  distinctly  to  the  intellectual  tastes  of  the  public,  or  devoted 
to  subjects  in  which,  the  public  welfare  or  public  culture  is  concerned. 

Subscription,  $3.00  per  annum ;  tingle  copy,  25  cents,  post-paid.  Binding-cases,  50  cents  each. 
Specimen  copy,  18  cents. 


The  Popular  Science  Monthly. 

Conducted  by  E.  L.  and  W.  J.  YOTJMANS. 

With  the  number  for  January,  1879,  Thk  Popular  Science  Monthly  was  permanently  enlarged 
to  144  pages.  Its  readers  will  thus  receive  sixteen  pages  additional  matter  without  increase  of 
price,  and  the  editors  will,  at  the  same  time,  he  enabkd  to  make  it  a  more  complete  exponent  of 
current  scieotific  thought.  The  contents  of  the  magazine  will,  as  heretofore,  consist  of  original 
scientific  articles  from  eminent  home  and  foreign  writers,  selections,  falling  within  its  scope,  from 
the  leading  English  periodicals,  translations  from  foreign  languages,  synopses  of  important  scien- 
tific papers,  and  notes  of  the  progress  of  science  throntrhout  the  world. 

The  Popular  Soiencb  Monthly  is  a  large  octavo,  handsomely  printed  on  clear  type,  and,  when 
necessary  to  further  convey  the  ideas  of  the  writer,  fully  illustrated. 

Tkbus  :  $5.00  per  annum,  or  50  cents  per  number.  Postage  prepaid.  Binding-cases  for  any 
volume  will  be  forwarded  by  mail,  post-paid,  upon  receipt  of  50  cents.    Specimen  copy,  35  cents. 


The   North  American  Review. 

PUBLISHED   MONTHLV. 

TblB  old  and  valued  periodical,  under  new  and  energetic  management,  has  during  the  past  year 
stepped  into  the  front  rank  of  literature,  showing  itself  the  equal.  If  not  the  superior,  of  the  great 
Reviews  and  Quarterlies  of  the  Old  World.    Per  annum,  $5.00  ;  per  number,  50  cents. 

D.  APPLETON  &  CO.,  Publishees. 


TO  THE   MEDICAL   PROFESSION. 


We  beg  to  call  your  attention  to  the  merits  of  the 
New  York  Medical  Journal.  In  doing  so,  we  can 
say  with  confidence  that  this  journal  occupies  a  higher 
place  in  medical  literature  than  any  other  monthly  pub- 
lication in  this  country,  and  that  henceforth  no  effort 
will  be  spared  to  enhance  its  value,  and  render  it  indis- 
pensable to  every  practitioner  who  desires  to  keep  up 
with  the  times.  Trusting  you  will  favor  us  with  your 
support, 

We  are,  yours  truly, 

D.  APPLETON  &  CO. 


The  foremost  Ajnerican  Monthly, 


THE 

New  York  Medical  Journal, 

Edited  by  JAMES   B.  HUNTER,  M.D., 

Surgeon  to  the  New  York  State  Woraan's  Hospital ;  Consulting  Surgeon  to  the  New  York  . 
Inflrmai-y  for  Women  and  Children ;  Member  of  the  New  York  Obstetrical  Society,  etc. 

The  leading  fmtwts  of  tlm  Journal  are  the  following: 

Original  Communications  from  Eminent  Members  of  the  Profession. 

Reports  of  Interesting  Cases  in  Private  Practice. 

Notes   of   Practice    in    Metropolitan    Hospitals,   illustrating   the   Use    of    New 

Methods   and   New   Remedies. 
Translations  and  Extracts  giving  the  Cream  of  all  the  Foreign  Journals. 
Reports  on  Medicine,  Surgery,  Obstetrics,  Gynaecology,  Laryngology,  PAXHOLoqT,  etc. 
Critical  and  Impartial  Reviews  of  all  New  Medical  Books. 
Proceedings  of  Medical  Societies. 
Copious  Illustrations  by  means  of  Woodcuts. 
The  Latest  General  Medical  Intelligence. 

A  new  volume  of  the  New  York  Medical  Journal  begins  with  the  nnmberB  for 
January  and  July  each  year.     Subscriptions  received  for  any  period. 

Terms,  $4.00  per  Annum,  postagre  prepaid  by  the  Publishers. 

Trial  Subscriptions  will  be  received  at  the  following  rates:  Three  months,  $1.00;  six 
months,  $2.00 ;  specimen  copy,  2.o  cents. 

A  General  Index  to  the  New  York  Medical  Journal,  from  its  first  issue  to  June, 
1876 — including  twenty-three  volumes — now  ready.     Price,  in  cloth,  75  cents,  post-paid. 

Hemittances,  invariahly  in  advance,  should  be  made  to 

D.  APPLETON  &  CO.,  Publishers,  549  &  551  Broadway,  N.  Y. 


S^'Mf-T-' if  ,g#4£ 


<r 


^^ 


c? 


1^1^ 


^  ^f'^/.r,  ^^^j^^^ce  <-^. 


